Process for manufacturing polyene esters and acids

ABSTRACT

A process for the manufacture of polyene esters or polyene acids comprises reacting a polyene O,O-dialkylacetal of di(O,O-dialkylacetal) with a vinylketene acetal or analogue thereof in the presence of a Lewis acid, hydrolyzing the reaction mixture depending on the vinylketene acetal used, subsequently cleaving alcohol under strongly basic conditions from the polyene derivative produced at this stage and, where the desired ester or carboxy group is still not present, performing the respective conversion. Certain intermediates in this process form a further aspect of the invention. The final products are primarily carotenoids which can be used appropriately, e.g. as colorants and pigments for foodstuffs, animal products etc.

BACKGROUND OF THE INVENTION

1. Field

The present invention relates to a novel process for manufacturingpolyene esters and acids from acetalized polyene aldehydes via anacid-catalyzed condensation reaction with vinylketene acetals.

2. Description

Lewis acid-catalyzed additions of α,β-unsaturated ethers (enol ethers)to acetals have been known for a long time and date back to the work ofMuller-Cunradi and Pieroh (see U.S. Pat. No. 2,165,962). Hoaglin andHirsch J.A.C.S. 71: 3468 (1949)! investigated this reaction further andbroadened the possible applications, which Isler et al. likewise did inthe 1950's with respect to the synthesis of β-carotene, crocetindialdehyde, lycopene as well as β-apocarotenoids see Helv. Chim. Acta,39: 249 et seq. and 463 et seq. (1956), ibid., 42: 854 et seq. (1959) aswell as U.S. Pat. Nos. 2,827,481 and 2,827,482!. Later, Mukaiyama Angew.Chem., 89: 858 et seq. (1977) and Org. Reactions, 28: 203 et seq.(1982)! extended the reaction by using the readily accessibletrimethylsilyl enol ethers.

The first Lewis acid-catalyzed condensations of 1-alkoxy-1,3-dienes(dienol ethers) with α,β-unsaturated acetals were reported by Nazarovand Krasnaya J. Gen. Chem. USSR, 28: 2477 et seq. (1958)! and by MakinPure & Appl. Chem., 47: 173 et seq. (1976), J.

Gen. Chem. USSR, 31: 3096 et seq. (1961) and 32: 3112 et seq. (1962)!.Here, the coupling of the acetal to the dienol ether takes place as faras can be seen exclusively at its γ-position with the formation of achain-lengthened α,β-unsaturated acetal, which, however, in competitionwith the first acetal reacts with further dienol ether to form afurther, chain-lengthened α,β-unsaturated acetal etc. telomer formation;see also Chemla et al., Bull. Soc. Chim. Fr., 130: 200 et seq. (1993)!.For this reason such a condensation has been found unworkable forsynthetic purposes, especially for the synthesis of apocarotenoids Isleret al., Adv. Org. Chem., 4: 115 et seq. (1963)!.

Not only 1-alkoxy-1,3-dienes, but also trimethylsilyloxydienes of thetype CH₂ ═CH--CH═CH--OSi(CH₃)₃ ! can be condensed with acetals in thepresence of Lewis acid catalysts, as disclosed by Mukaiyama et al. inChem. Lett. 1975, 319 et seq. In this coupling too the attack takesplace exclusively at the terminal (γ-) carbon atom of the diene systemin order to form "γ-products" see Mukaiyama et al., Bull. Chem. Soc.Jap, 50: 1161 et seq. (1977) and Japanese Patent Publication (Kokai)36,645/1977!. In contrast to the reaction with 1-alkoxy-1,3-dienes, inthe case of the reaction of trimethylsilyloxydienes with acetals thereis formed an aldehyde which does not react further with the diene (notelomer formation). By using this method Mukaiyama et al. were able tosynthesize vitamin A see Kokai, 36,645/1977, Chem. Lett. 1975, 1201 etseq. and Bull. Chem. Soc. Japan, 51: 2077 et seq. (1978)! and workersfrom Rhone-Poulenc developed new routes to carotenoids and vitamin A(see DOS 2,701,489 and A.E.C. Societe de Chimie Organique et BiologiqueNo. 7824350).

Silylated vinylketene acetals of the type CH₂═CH--CH═C-(Oalkyl)(OSi(CH₃)₃)! can also react with acetals in a manneranalogous to the aforementioned trimethylsilyloxydienes see Tetr. Lett.,20: 3209 et seq. (1979) and Chimia, 34: 265 et seq. (1980)!. As evidentfrom, among others, Tetr. Lett., 22: 2833 et seq. (1981), ibid. 26: 397et seq. (1985), DOS 3,244,273 and U.S. Pat. No. 4,937,308, the knownreactions always formed not readily separable mixtures of the twopossible γ- and a-coupling products "γ-products" . . . CH(Oalkyl¹)--CH₂--CH═CH--COOalkyl² ; "α-products" . . .CH(Oalkyl¹)--C(CH₃)(CH═CH₂)--COOalkyl² !, rendering this reaction--atbest marginally usable for synthetic purposes in the carotenoid field.This reaction would be interesting and useful only if completeγ-selectivity could be achieved, for example for the synthesis ofpolyenes, namely apoesters, crocetin esters etc.; because by eliminationof the alcohol alkyl¹ OH from the γ-product it is possible to form, ifdesired, a further (conjugated) double bond with the formation of theproduct . . . CH═CH--CH═CH--COOalkyl². Thus, such polyenes could beproduced without employing the Wittig or Horner reaction hitherto usedfor this purpose.

SUMMARY OF THE INVENTION

The present invention provides a process for manufacturing a compound offormula: ##STR1## wherein A is a monovalent conjugated polyene group ora methyl-substituted, monovalent conjugated polyene group,

B is a bivalent conjugated polyene group or a methyl-substituted,bivalent conjugated polyene group,

R¹ and R² each independently is hydrogen or methyl, and

R³ is hydrogen or C₁₋₆ -alkyl, with the --CH═CH--C(R¹)═C(R²)--COOR³group(s) in each case being situated in the terminal position(s) of theconjugated chain of group A or B.

This process comprises reacting a compound of formula:

    A--CH(OR.sup.4).sub.2                                      II'

or

    (R.sup.4 O).sub.2 HC--B--CH(OR.sup.4).sub.2                II"

wherein

A and B are as above, with the --CH(OR⁴)₂ group(s) being situated in theterminal position(s) of the conjugated chain of group A or B, and

R⁴ is C₁₋₆ -alkyl, with a compound of formula: ##STR2## wherein R¹ andR² are as above, and

R⁵ is C₁₋₆ -alkyl and

R⁶ is C₁₋₆ -alkyl or tri(C₁₋₆ -alkyl)silyl, or R⁵ and R⁶ both aretri(C₁₋₆ -alkyl)silyl, or R⁵ and R⁶ together form 1,2-ethylene or1,3-trimethylene, in the presence of a Lewis acid, and where a compoundof formula III in which R⁵ and R⁶ both are C₁₋₆ -alkyl or both aretri(C₁₋₆ -alkyl)silyl or together form 1,2-ethylene or 1,3-trimethyleneis used, subsequently hydrolyzing the compound formed, so as to form inall cases a compound of the formula: ##STR3## wherein A, B, R¹, R² andR⁴ are as above, with the --CH(OR⁴)--CH₂ --C(R¹)═C(R²)COOR⁷ group(s)being situated in the terminal position(s) of the conjugated chain ofgroup A or B, and

R⁷ is C₁₋₆ -alkyl, hydrogen, 2-hydroxyethyl or 3-hydroxy-n-propyl.

The R⁴ OH group is then cleaved from the compound of formula IV' or IV"under strong basic conditions, and where there is a difference betweengroups --COOR⁷ and --COOR³, the group --COOR⁷ is converted to group--COOR³.

Unique compounds provided by the present invention include compounds ofthe formula: ##STR4## wherein A is a monovalent conjugated polyene groupor a methyl-substituted, monovalent conjugated polyene group,

B is a bivalent conjugated polyene group or a methyl-substituted,bivalent conjugated polyene group,

R¹ and R² each independently is hydrogen or methyl, R⁴ is C₁₋₆ -alkyl,and

R⁷ is C₁₋₆ -alkyl, hydrogen, 2-hydroxyethyl or 3-hydroxy-n-propyl, withthe --CH(OR⁴)--CH₂ --C(R¹)═C(R²)--COOR⁷ group(s) in each case beingsituated in the terminal position(s) of the conjugated chain of group Aor B.

Another unique series of compounds include compounds of the formula:##STR5## wherein R¹ and R² each independently is hydrogen or methyl andR^(5") and R^(6") each independently is C₁₋₆ -alkyl, with the exceptionof 1,1-dimethoxy-1,3-butadiene and 1,1-diethoxy-3-methyl-1,3-butadiene.

Further unique compounds include compounds of the formula: ##STR6##wherein R¹ and R² each independently is hydrogen or methyl, and s is 2or 3, with the exception of 2-allylidene- 1,3!dioxolane,2-(1-methyl-allylidene)- 1,3!dioxolane and 2-(2-methyl-allylidene)-1,3!-dioxolane.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will now be described in terms of its preferredembodiments. These embodiments are set forth to aid in understanding theinvention, but are not to be construed as limiting.

An object of the present invention is to manufacture, starting frompolyene (di)acetals and vinylketene acetals or silylated analoguesthereof, correspondingly chain-lengthened polyene (di)esters or acidswhile avoiding as far as possible the aforementioned disadvantages ofthe state of the art and replacing the Wittig or Horner reactionhitherto used for this purpose.

This object is achieved in accordance with the invention by reacting apolyene (di)O,O-dialkyl acetal with a vinyl-O,O-dialkyl- orO,O-alkylene-ketene acetal or an O-mono- or O,O-disilylated analoguethereof in the presence of a Lewis acid to give the correspondinglychain-lengthened (bis)δ-alkoxy-γ,δ-saturated polyene ester or thecorresponding (di)acid and subsequently eliminating the δ-positionedalkanol from the thus-formed (di)ester or from the corresponding(di)acid under basic conditions in order to obtain the desired(conjugated) polyene (di)ester or the corresponding (di)acid. Not onlyis the reaction of the vinyl-O,O-dialkyl- or vinyl-O,O-alkylene-keteneacetal or of the O-mono- or O,O-disilylated analogue with the polyeneO,O-dialkyl acetal novel, but surprisingly it takes place (so far as canbe seen) with exclusive attack at the y-position of the vinylketeneacetal derivative. By the subsequent base-induced elimination of thealkanol a (conjugated) C--C double bond is formed without requiring aphosphorus-containing or silicon-containing reagent, which is incontrast to the methodology hitherto usually used in this field.

Accordingly, the present invention is concerned with a process for themanufacture of a polyene ester or a polyene acid of the formula ##STR7##wherein A signifies an optionally methyl-substituted, monovalentconjugated polyene group,

B signifies an optionally methyl-substituted, bivalent conjugatedpolyene group,

R¹ and R² each signify hydrogen or methyl and

R³ signifies hydrogen or C₁₋₆ -alkyl, with the--CH═CH--C(R¹)═C(R²)--COOR³ group(s) in each case being situated in theterminal position(s) of the conjugated chain of group A or B, whichprocess comprises reacting a polyene (di)O,O-dialkyl acetal of theformula

    A--CH(OR.sup.4).sub.2                                      II'

or

    (R.sup.4 O).sub.2 HC--B--CH(OR.sup.4).sub.2                II"

wherein

A and B have the significances given above, with in this case the--CH(OR⁴)₂ group(s) being situated in the terminal position(s) of theconjugated chain of group A or B and

R⁴ signifies C₁₋₆ -alkyl, with a vinylketene acetal or analogue thereofof the formula ##STR8## wherein R¹ and R² have the significances givenabove and

R⁵ signifies C₁₋₆ -alkyl and

R⁶ signifies C₁₋₆ -alkyl or tri(C₁₋₆ -alkyl)silyl or R⁵ and R⁶ bothsignify tri(C₁₋₆ -alkyl)silyl or R⁵ and R⁶ together form 1,2-ethylene or1,3-trimethylene, in the presence of a Lewis acid, hydrolyzing thereaction mixture where a vinylketene acetal of formula III in which R⁵and R⁶ both signify C₁₋₆ -alkyl or both signify tri(C₁₋₆ -alkyl)silyl ortogether form 1,2-ethylene or 1,3-trimethylene is used, subsequently (inall cases) cleaving off the alcohol R⁴ OH under strong basic conditionsfrom the thus-produced compound of the formula ##STR9## wherein A, B,R¹, R² and R⁴ have the significances given above, with in this case the--CH(OR⁴)--CH₂ --C(R¹)═C(R²)COOR⁷ group(s) being situated in theterminal position(s) of the conjugated chain of group A or B, and

R⁷ signifies C₁₋₆ -alkyl, hydrogen, 2-hydroxyethyl or3-hydroxy-n-propyl, and, where there is a difference between group(s)--COOR⁷ and --COOR³, converting the former into the latter.

The process in accordance with the invention can in principle be used inthe case of all of the aforementioned polyene O,O-dialkyl acetals offormula II' or polyene di(O,O-dialkyl acetals) of formula II' which havethe acetal group --CH(OR⁴)₂ at the end or at both ends of the polyenechain. Among such educts there are to be found, inter alia, thefollowing sub-classes with the abbreviated form of presentation which isusual in carotenoid chemistry (using simple lines) being used for thestructural formulas!:

Alicyclic-aliphatic polyene O,O-dialkyl acetals, which mainly belong tothe carotenoid field as acetals of asymmetric carotenoid aldehydeshaving a six-membered (cyclohexene) ring!, of the formula ##STR10##wherein R⁴ has the significance given above and

R⁸ and R⁹ each independently signify hydrogen, an optionally protectedhydroxy group or an optionally protected oxo group,

m signifies 0, 1, 2, 3 or 4 and

n signifies 0 or 1,

which, after carrying out the multistage process in accordance with theinvention, are converted into the corresponding alicyclic-aliphaticpolyene esters or acids of the formula ##STR11##

aliphatic polyene O,O-dialkyl acetals, which likewise mainly belong tothe carotenoid field (as acetals of open-chain asymmetric carotenoidaldehydes), of the formula ##STR12## wherein R⁴ has the significancegiven above and

p signifies 0, 1 or 2,

q signifies 0, 1, 2 or 3 and

n signifies 0 or 1,

which, after carrying out the multistage process in accordance with theinvention, are converted into the corresponding aliphatic polyene estersor acids of the formula ##STR13##

aliphatic polyene di(O,O-dialkyl acetals), which likewise mainly belongto the carotenoid field (as acetals of symmetrical carotenoiddialdehydes), of the formula ##STR14## wherein R⁴ has the significancegiven above and

r signifies 0, 1 or 2 and

n signifies 0 or 1, which, after carrying out the multistage process inaccordance with the invention, are converted into the correspondingaliphatic polyene diesters or diacids of the formula ##STR15##

The educts of formulas IIa, IIb and IIc can be embraced by formula II:

    R--CH(OR.sup.4).sub.2                                      II

wherein

R signifies a group (a), (b) or (c) ##STR16## and R⁴, R⁸, R⁹, m, n, p, qand r have the significances given above.

After carrying out the multistage process in accordance with theinvention the educt of formula II is converted into the correspondingproduct of formula I: ##STR17## wherein R' has the significance of Rgiven above, with the dialkoxymethyl group (R⁴ O)₂ HC-- being replacedby the group R³ OOC--C(R²)═C(R¹)--HC═HC-- where R' signifies a group(c).

Formula I then embraces formulas Ia, Ib and Ic.

Where the product of formula I, especially of formula Ia, has one or twoprotected groups (R⁸, R⁹) on the cyclohexene ring, the protectinggroup(s) present can, if desired, be cleaved off, which represents afurther aspect of the present invention.

In the scope of the present invention the term "C₁₋₆ -alkyl" embracesstraight-chain and branched groups such as, for example, methyl, ethyland isobutyl. This applies to the C₁₋₆ -alkyl group of a groupcontaining this, e.g. tri(C₁₋₆ -alkyl)silyl.

The term "protected hydroxy group" embraces usual protected hydroxygroups (especially those which are familiar from the carotenoid field),particularly etherified hydroxy groups and acyloxy groups. The"etherified hydroxy groups" are, for example, C₁₋₅ -alkoxy groups,preferably methoxy and ethoxy; C₂₋₁₆ -alkoxyalkoxy groups, preferably1-methoxy-1-methylethoxy; arylalkoxy groups, preferably benzyloxy;tetrahydropyranyloxy; and tri(C₁₋₅ -alkyl)silyloxy groups, preferablytrimethylsilyloxy. The acyloxy groups embrace especially alkanoyloxy andaroyloxy groups with up to 8 carbon atoms such as, for example,formyloxy, acetoxy, propionyloxy and benzoyloxy.

The term "protected oxo group" also embraces usual protected oxo groups(especially those which are familiar from the carotenoid field).Acetalized oxo groups, especially those in which the term protected oxostands for two C₁₋₅ -alkoxy groups (e.g. two methoxy groups) or for aC₂₋₆ -alkylenedioxy group (e.g. ethylenedioxy or 2,3-butylenedioxy) arepreferred. Further, an oxo group can also be protected as an enol ether,primarily in the case of α-hydroxy-ketones (e.g. R⁸ and R⁹ signifyhydroxy or oxo or vice versa), whereby the etherification of the enediolcan preferably also be effected by the formation of a cyclic acetal orketal (e.g. with acetone to the acetonide). The oxo group can also beprotected, for example, as an imine.

The formulas of polyenes disclosed in the scope of the present inventionembrace in each case isomeric forms, e.g. optically active and cis/transor E/Z isomers, as well as mixtures thereof unless indicated to thecontrary. The carbon atom carrying the residue R⁸ or R⁹ where R⁸ or R⁹signifies an optionally protected hydroxy group (see formulas Ia andIIa) can be mentioned as an example of a chiral (optically active)centre. With respect to E/Z isomerism, then there are generallypreferred the (all-E) isomers of the educts and of the products of theprocess in accordance with the invention.

The first process step of the process in accordance with the inventionis conveniently carried out by reacting the polyene (di)O,O-dialkylacetal of formula II' or II" with the vinylketene acetal (analogue) offormula IlIl in an organic solvent at temperatures in the range of about-40° C. to about 100° C., preferably in the temperature range of about-20° C. to room temperature, and in the presence of a Lewis acid.Suitable organic solvents are, in general, all aprotic polar ornon-polar solvents. Especially preferred among such solvents are loweraliphatic and cyclic hydrocarbons, e.g. n-pentane, n-hexane andcyclohexane; lower, halogenated aliphatic hydrocarbons, e.g. methylenechloride and chloroform; lower aliphatic and cyclic ethers, e.g. diethylether, tert.butyl methyl ether and tetrahydrofuran; lower aliphaticnitriles, e.g. acetonitrile; as well as aromatics, e.g. toluene.Examples of Lewis acids which can be used are zinc chloride, zincbromide, titanium tetrachloride, lithium perchlorate, boron trifluorideetherate as well as iron(III) chloride; these are generally used incatalytic amounts, conveniently in an amount of between about 0.1 and 10mol percent based on the amount of polyene (di)O,O-dialkyl acetalemployed and preferably in a mol percent range of 1 to 3. Moreover,about 1.1 to about 1.6 equivalents, preferably about 1.3 to about 1.4equivalents, of vinylketene acetal (analogue) are conveniently used perequivalent of polyene (di)O,O-dialkyl acetal. Furthermore, the reactionis conveniently effected at normal pressure, although generally thepressure is not critical.

Where a vinylketene acetal of formula III in which R⁵ and R⁶ bothsignify C₁₋₆ -alkyl or together form 1,2-ethylene or 1,3-trimethylene isused, a compound of formula IV' or IV" is not produced after reactingthe polyene (di)O,O-dialkyl acetal of formula II or II' with thisvinylketene acetal, but instead there is produced an intermediate of theformula ##STR18## wherein A, B, R¹, R² and R⁴ have the significancesgiven above and R^(5') and R^(6') both signify C₁₋₆ -alkyl or togetherform 1,2-ethylene or 1 ,3-trimethylene.

Also when a vinylketene acetal of formula III in which R⁵ and R⁶ bothsignify tri(C₁₋₆ -alkyl)silyl is used, a compound of formula IV' or IV"is not produced after reaction of the polyene (di)O,O-dialkyl acetal offormula II' or II" with this vinylketene acetal, but instead in thiscase there is produced an intermediate of the formula ##STR19## whereinA, B, R¹, R² and R⁴ have the significances given above.

If desired, the respective intermediate can be isolated from thereaction mixture and subsequently hydrolyzed to the correspondingcompound of formula IV' or IV" in which R⁷ in each case signifies C₁₋₆-alkyl (R^(5') and R^(6') both signify C₁₋₆ -alkyl), 2-hydroxyethyl or3-hydroxy-n-propyl (R^(5') and R^(6') together form 1,2-ethylene or1,3-trimethylene) or hydrogen (starting from the 1 5 intermediate offormula V"' or V"")!. However, it has been found to be convenient not toundertake such an isolation and subsequent hydrolysis, but to hydrolyzethe intermediate in the reaction mixture immediately after completion ofthe reaction II'/II"+III→V'/V"/V"'//V"" in order in these cases toproceed to the compound of formula IV' or IV" (hereinafter abbreviatedto IV'/IV"). Starting from an intermediate of formula V' or V" thehydrolysis can be suitable effected by adding to the reaction mixture anaqueous solution of a weak acid, preferably slightly diluted aqueousacetic acid, and subsequently stirring the mixture for a time, forexample about 30 minutes to about 2 hours, conveniently in thetemperature range of about 0° C. to room temperature. In the other case,i.e. starting from an intermediate of formula V"' or V"", the hydrolysistakes place much more readily, namely with water alone; the hydrolysiscan even be effected in the course of the normal working-up, wherebywater is mainly used as the purifying agent.

Depending on the vinylketene acetal (analogue) of formula III which isused there is obtained, after carrying out the first process step aswell as any hydrolysis which may be required, as explained in moredetail above, the corresponding product of formula IV'/IV", namely:

after using a vinylketene acetal (analogue) of formula III in which R⁵signifies C₁₋₆ -alkyl and R⁶ signifies C₁₋₆ -alkyl or tri(C₁₋₆-alkyl)silyl, a compound of formula IV'/IV" in which R⁷ signifies C₁₋₆-alkyl (when R⁶ signifies tri(C₁₋₆ -alkyl)silyl, this group iseliminated);

after using a vinylketene acetal analogue of formula III in which R⁵ andR⁶ both signify tri(C₁₋₆ -alkyl)silyl, a compound of formula IV'/IV" inwhich R⁷ signifies hydrogen both tri(C₁₋₆ -alkyl)silyl groups areeliminated and the product has one or two terminal 4-carboxy-1-(C₁₋₆-alkoxy)-3-butenyl group(s) or corresponding 3- and/4-methyl substituted(R¹ and/or R² =methyl) group(s) --CH(OR⁴)--CH₂ --C(R¹)═C(R²)--COOH!; and

after using a vinylketene acetal of formula III in which R⁵ and R⁶together form 1,2-ethylene or 1,3-trimethylene, a compound of formulaIV'/IV" in which R⁷ signifies 2-hydroxyethyl or 3-hydroxy-n-propyl.

The respective product can be isolated from the reaction mixture and, ifdesired, purified in a manner known per se. Typically, the mixture iscombined with water and the batch is extracted with a water-immiscibleorganic solvent such as, for example, with a lower alkane or dialkylether, e.g. n-hexane or tert.butyl methyl ether, and the organic phaseis washed with water and/or saturated aqueous sodium chloride and/orsodium bicarbonate solution, dried and concentrated. The thus-isolatedand at least to some extent washed crude product can then, if desired,be purified further, for example by column chromatography, e.g. usingeluents such as n-hexane, ethyl acetate, toluene or mixtures thereof, or(re)crystallization, for example from an alcohol, e.g. methanol orethanol. Alternatively, and often preferably, the crude product takenup, for example, in a lower alkanol can be reacted directly in the lastprocess step (cleavage of the alcohol R⁴ OH) of the present invention,i.e. in the sense of a "through process" II'/II"+III→IV'/IV"→I'/I".

The last process step is conveniently carried out by subjecting thecompound of formula IV'/IV" dissolved in a suitable organic solvent tostrongly basic conditions, i.e. reacting it in the presence of a basewith cleavage of the alcohol R⁴ OH to the corresponding polyene ester oracid. Suitable organic solvents are, in general, polar or non-polarsolvents such as, for example, alcohols, aliphatic or cyclic ethers,e.g. diethyl ether and tetrahydrofuran, and aliphatic esters, e.g. ethylacetate; or, respectively, aromatics, e.g. toluene, aliphatichydrocarbons, e.g. n-hexane, and lower halogenated aliphatichydrocarbons, e.g. methylene chloride, chloroform and carbontetrachloride; or also mixtures of an alcohol with another solventmentioned here. Where an alcohol of the formula R³ OH in which R³ isdifferent from R⁷ (as C₁₋₆ -alkyl, 2-hydroxyethyl or 3-hydroxy-n-propyl)in the compound of formula IV'/IV" is used as the solvent, the finalproduct of formula I' or I" has the respective ester group --COOR³ as aresult of the excess amount of alcohol R³ OH vis-a-vis thisintermediate: in this (quite simple) manner, i.e. bytransesterification, the ester group --COOR⁷ is converted into the estergroup --COOR³ which is different therefrom. Otherwise, a separatetreatment, i.e. trans-esterification of the isolated product which hasthe ester group --COOR⁷ is carried out in a manner known per se in orderto convert the group --COOR⁷ into the desired ester group --COOR³ whichis different therefrom.

The base which is used can be inorganic or organic, there being suitablein general strong bases such as, for example, alkali metal alcoholates,especially sodium methylate, sodium ethylate, potassium methylate,potassium ethylate and potassium tert.butylate, as well as alkali metalhydrides, especially sodium hydride.

Conveniently, at least one equivalent of base, preferably about 1.5 toabout 2 equivalents, is used per equivalent of the compound of formulaIV' or IV". The reaction is suitably effected in a temperature range ofabout 0° C. to about 100° C., preferably at temperatures of about roomtemperature to about 50° C. Moreover, the reaction is convenientlyeffected at normal pressure, although in general the pressure is notcritical.

It has been found to be especially advantageous to carry out the lastprocess step using a sodium alkoxide as the base and the correspondingalkanol as the solvent at temperatures between room temperature and thereflux temperature of the respective reaction mixture, preferably in atemperature range of about 40° C. to about 60° C. Conveniently, either asolution of the sodium alkoxide in the alcohol is prepared in advance orthis solution is prepared freshly from metallic sodium and the alkanol.The bringing together of the alkanolic solution of the sodium alkoxidewith the solution of the compound of formula IV'/IV" in the (same)alkanol, preferably likewise previously prepared, can be effected in anysequence and preferably at room temperature. Then, the reaction mixtureis subsequently stirred for several hours and the reaction has normallyfinished at the the latest after 24 hours.

Irrespective of the chosen procedure for the last process step, theproduct can be isolated from the reaction mixture and purified in amanner known per se. The respective working-up normally comprisesneutralization of the remaining base by addition of an organic orinorganic acid such as, for example, a carboxylic acid, e.g. aceticacid, or an aqueous mineral acid, e.g. dilute sulphuric acid.

In the particular embodiment of the procedure described above using asodium alkoxide as the base, after completion of the reaction themixture is conveniently cooled to room temperature or even to about 0°C. and thereafter preferably neutralized with aqueous acetic acid, whichnormally leads to (possibly further) crystallization of the product offormula I' or I". The crystallization can also be expedited by furthercooling. After its isolation, suitably by filtration, the product can bewashed, for example with water and/or aqueous alcohol, and finallydried, optionally under reduced pressure. If desired, further methodssuch as, for example, column chromatography and recrystallization can beemployed in order to provide an even purer product.

The cleavage of the alcohol R⁴ OH from the compound of formula IV'/IV"can also be effected under acidic conditions in order to serve as analternative to the last process step of the process in accordance withthe invention which is effected under strongly basic conditions. Afterpertinent experiments to bring about this cleavage using catalyticamounts of a strong acid, e.g. p-toluenesulphonic acid, it has beenestablished that the cleavage actually proceeds relatively readily. Forexample, when using 12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acidethyl ester with a catalytic amount of p-toluenesulphonic acid inmethylene chloride at about 0° C. the cleavage of methanol was effectedafter about 30 minutes and gave crude 8'-apo-β-carotenoic acid ethylester in almost quantitative yield by weight. According to HPLC thecrude product consisted to the extent of about 71.5% of the. (all E)isomer and of several additional presumably (Z)! isomers. The absolutecontent of the crude product was, however, only about 37.5% according toHPLC. Possibly, a partial polymerization of the polyene system takesplace under such strongly acidic conditions. Further attempts tooptimise this acid-catalyzed cleavage brought no improved results.Surprisingly, it was established that the cleavage effected under basicconditions leads almost exclusively to the desired (all E) isomer, withalmost no (Z) isomers and further undesired isomers being formed.

Depending on the compound of formula IV' or IV" and solvent (alcoholicor other solvent) used there is obtained after carrying out the lastprocess step the product of formula I' or I" (abbreviated hereinafter toI'/I"), respectively, appropriate to the residue R³. Where the solventis not an alcohol (so that no trans-esterification can then take place),there is obtained:

after using a compound of formula IV'/IV" in which R⁷ signifies C₁₋₆-alkyl, a polyene ester/diester of formula I'/I" in which R³ signifiesthe corresponding C₁₋₆ -alkyl;

after using a compound of formula IV'/IV" in which R⁷ signifieshydrogen, a polyene acid/diacid of formula I'/I" in which R³ signifieshydrogen; and

after using a compound of formula IV'/IV" in which R⁷ signifies2-hydroxyethyl or 3-hydroxy-n-propyl, a polyene ester/diester of formulaI'/I" in which R³ does not have the significance hitherto given, butsignifies 2-hydroxyethyl or 3-hydroxy-n-propyl.

In each of the above three cases the residue R⁷ remains unaltered in thecourse of the last process step.

On the other hand, where an alcohol, especially a C₁₋₆ -alkanol, is usedas the solvent and when the three types of compounds IV'/IV" are used, atrans-esterification takes place in two cases (in the first and thirdcase) as already indicated above. In this manner there is formed in eachcase a polyene ester of formula I'/I" in which R³ corresponds to therespective alkyl residue of the alkanol: the group --COOR⁷ in thecompound IV'/IV" is thus converted without particular measures into thegroup --COOR³ which is different therefrom, unless the alcoholic solventcorresponds to the alcohol R⁷ OH. The use of the respective alkanol R³OH is preferred for this reason and also because the product of formulaI, which is difficultly soluble in the alcohol, crystallizes out fromthe solution already during the reaction.

If desired, protecting groups (R⁸ and/or R⁹ as a protected hydroxy oroxo group) which may be present in the product of formula I' or I"obtained can be cleaved off according to methods known per se, e.g. byhydrolysis with acid or base.

While some of the educts of the process in accordance with the inventionare known, other precursors, which are in part known, can be producedaccording to methods known per se.

Thus, for example, the polyene O,O-dialkyl acetals of formula II' andthe polyene di(O,O-dialkyl acetals) of formula II" can be produced veryreadily in a generally known manner by reacting the polyene monoaldehydeof the formula A--CHO or polyene dialdehyde of the formula OHC--B--CHOwith the respective trialkyl orthoformate, especially in thecorresponding C₁₋₆ -alkanol, e.g. methanol for the O,O-dimethyl acetal,and in the presence of a catalytic amount of an organic acid or a Lewisacid, e.g. p-toluenesulphonic acid or zinc chloride (see, for example,Organikum, Organisch-chemisches Grundpraktikum, 6th edition, p. 377 etseq. (1963)!. The reaction takes place in suspension, i.e. therespective polyene monoaldehyde or dialdehyde is suspended in thealkanol and then conveniently about two or four mol equivalents,respectively, of the trialkyl orthoformate are added to the suspension,followed by a trace of acidic catalyst, e.g. p-toluenesulphonic acid.Thereby, the monoaldehyde or dialdehyde dissolves slowly and the polyeneO,O-dialkyl acetal or di(O,O-dialkyl acetal) of formula II'/II"simultaneously crystallizes out slowly. The reaction is convenientlycarried out in a temperature range of about 0° C. to about 40° C., andas a rule takes about 2 to about 4 hours. As further literature sourceswhich illustrate the generally known acetalization method reference ismade to European Patent Publication Nos. 0 252 389 and 0 391 033 as wellas to J. Mol. Cat., 79: 117 et seq. (1993).

The polyene monoaldehydes A--CHO and dialdehydes OHC--B--CHO in turn areeither known, especially from the technical literature concerningcarotenoids, or--where novel--can be produced according to methods knownper se. Thus, for example, the reaction of various C₁₅ -Wittig saltswith 2,7-dimethyl-2,4,6-octatrienedial (the so-called "C₁₀ -dialdehyde")to give the corresponding monoaldehydes, the reaction of various C₅-Wittig aldehydes with long-chain polyene aldehydes likewise to givesuch monoaldehydes as well as the two-fold reaction of the C₁₀-dialdehyde with C₅ - or C₁₀ -Wittig aldehydes to give variousdialdehydes are known from this literature. The textbook "Carotenoids"(O. Isler, published by Birkhauser, Basel and Stuttgart, 1971),especially chapters VI and XII thereof and the further literaturementioned therein, provides much useful information relating to theproduction and the occurrence of the known monoaldehydes anddialdehydes. Where educts which have protected hydroxy, oxo or formylgroups are used, then such "protected" educts can be produced, forexample, directly from the corresponding unprotected educts according tomethods known per se.

The vinylketene acetals or analogues thereof of formula III are in partknown compounds; the majority of these educts are, however, novel.

Certain compounds of formula III in which R⁵ and R⁶ each independentlysignify C₁₋₆ -alkyl are known: these are especially1,1-dimethoxy-1,3-butadiene and 1,1-diethoxy-3-methyl-1,3-butadiene(formula III in which R¹ and R² both signify hydrogen and R⁵ and R⁶ bothsignify methyl and, respectively, R¹ signifies methyl, R² signifieshydrogen and R⁵ and R⁶ both signify ethyl). The remaining compounds ofthis sub-class are considered to be novel. All of these compounds can beproduced in accordance with the following Reaction Scheme starting froma nitrile of formula VI which is known or which can be producedaccording to methods known per se: ##STR20## wherein R¹ and R² have thesignificances given above and R^(5") and R^(6") each independentlysignify C₁₋₆ -alkyl.

The reaction of the nitrile of formula VI with the alkanol R^(5") OH inthe presence of gaseous hydrogen chloride gives the correspondingiminoalkyl ester of formula VII, which in most cases is present incrystalline form. An aprotic solvent, especially a lower aliphatichydrocarbon, e.g. n-pentane or n-hexane; a lower halogenated aliphatichydrocarbon, e.g. methylene chloride or chloroform; or a aromatic, e.g.benzene or toluene, is suitably used as the solvent. Both the alkanoland the hydrogen chloride are conveniently used in slight excess, namelyup to about 50%; preferably up to about 10 and, respectively, 20%(equivalents of alkanol and hydrogen chloride, respectively, relative toequivalents of nitrile). The reaction is suitably effected in atemperature range of about -20° C. to about +60° C., preferably in atemperature range of about 0° C. to room temperature.

The further reaction of the iminoalkyl ester with the alkanol R^(6") OH,which may if desired be different from the alkanol R^(5") OH, to givethe orthoester of formula VIII is conveniently effected in an aproticsolvent, e.g. one of the aforementioned solvents, and at temperatures inthe range of about 0° C. to about 60° C., preferably at roomtemperature.

One equivalent of alkanol R^(6") OH can be eliminated from theorthoester of formula VIII using sodium amide in liquid ammonia as thebase or solvent, with the desired vinylketene acetal of formula IIIabeing obtained very easily. Other base/solvent combinations can be usedfor this purpose, especially an alkali metal amide (generally) or analkali metal alkyl, e.g. butyllithium, in each instance in a polar orapolar aprotic solvent such as, for example, a lower aliphatichydrocarbon, e.g. n-hexane, a lower aliphatic ether, e.g. diethyl ether,or an aromatic, e.g. benzene or toluene.

Of those vinylketene acetal analogues of formula III in which R⁵signifies C₁₋₆ -alkyl and R⁶ signifies tri(C₁₋₆ -alkyl)silyl, at least1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (formula III inwhich R¹ signifies hydrogen, R² signifies methyl, R⁵ signifies ethyl andR⁶ signifies trimethylsilyl) is known see, inter alia, Tetr. Lett., 20:3209 et seq. (1979), Chimia, 34: 265 et seq. (1980) and Tetr. Lett., 26:397 et seq. (1985)!. Those analogues which are novel can be produced,for example, from the corresponding alkyl 3-butenoate by reaction withlithium diisopropylamide and the corresponding trialkylsilyl chloride atlow temperatures, e.g. about -70° C. see especially Tetrahedron, 40:3455 et seq. (1984)!. The aforementioned alkyl 3-butenoates (startingmaterials) are, in turn, known or can be produced according to methodsknown per se; ethyl 2-methyl-3-butenoate can be produced, for example,by ethanolysis of 2-methyl-3-butenenitrile (formula VI in which R¹signifies hydrogen and R² signifies methyl), a byproduct in thesynthesis of adiponitrile (Pinner reaction; see GermanOffenlegungsschrift 3,244,273, as well as U.S. Pat. No. 4,937,308).

A further sub-class of vinylketene acetals or analogues thereof offormula III likewise includes known compounds, e.g.1,1-di(trimethylsilyloxy)-2-methyl-1,3-butadiene formula III in which R¹signifies hydrogen, R² signifies methyl and R⁵ and R⁶ both signifytrimethylsilyl; see J.A.C.S., 110: 5841 et seq. (1988)!. In total, thissub-class consists of vinylketene acetal analogues of formula III inwhich R⁵ and R⁶ both signify tri(C₁₋₆ -alkyl)silyl. The aforementionedknown analogue can be produced, for example, starting from2-methyl-3-butenoic acid trimethylsilyl ester by deprotonization usinglithium diisopropylamide at about -75° C. and subsequent reaction withtrimethylsilyl chloride in accordance with the conditions given in J.Organomet. Chem., 338: 149 et seq. (1988). The remaining analogues ofthis type can be produced in a similar manner.

The remaining vinylketene acetals of formula III are novel compoundswith three exceptions. The exceptions are 2-alkylidene- 1,3!dioxolane,2-(1-methyl-allylidene)- 1,3!dioxolane and 2-(2-methyl-allylidene)-1,3!dioxolane (formula III in which R¹ and R² both signify hydrogen, R¹signifies hydrogen and R² signifies methyl or R¹ signifies methyl and R²signifies hydrogen, respectively, and R⁵ and R⁶ in each case togetherform 1,2-ethylene). The synthesis of the second-named compound ispublished in Tetrahedron, 50: 5109-5118 (1994); the acetal was producedin mg amounts starting from tiglic acid, but was not isolated and wasonly detected by ¹ H-NMR spectroscopy (capillary tube). Other relevantliterature sources concerning the three known vinylketene acetals are J.Chem. Soc., Perkin Trans., 1(5): 1582-4 (1981) and Macromolecules,28(12): 4319-4325 (1995).

In general, the vinylketene acetals of this particular sub-class, i.e.of formula III in which R⁵ and R⁶ together form 1,2-ethylene or1,3-trimethylene, can be produced in accordance with the followingReaction Scheme (as in the case of Reaction Scheme 1 starting from thenitrile of formula VI): ##STR21## wherein R¹ and R² have thesignificances given above and s signifies 2 or 3.

The hydrolysis of the nitrile of formula VI to the correspondingcarboxylic acid of formula IX and the subsequent esterification of thiscarboxylic acid to the ester of formula X can in each case be carriedout in a manner known per se see, for example, Organikum,Organisch-chemisches Grundpraktikum, 6th edition, p. 411 et seq. (1967)and, respectively, J. March, Advanced Organic Chemistry, 3rd edition, p.349 et seq. (1989)!. Then, the cyclization of the ester to the desired1,3!dioxolane or 1,3!dioxane can be conveniently effected in an aproticpolar or non-polar solvent, especially a lower aliphatic hydrocarbon,e.g. n-hexane, a lower aliphatic ether, e.g. diethyl ether, or anaromatic, e.g. toluene, in the presence of a strong base, especially analkali metal alkyl, e.g. methyllithium or butyllithium, an alkali metalhydride, e.g. sodium hydride or potassium hydride, or an alkali metalamide, e.g. lithium amide, sodium amide or potassium amide or lithiumdiisopropylamide, at temperatures in the range of about -70° C. to about+100° C., preferably in a temperature range of about -30° C. to about 0°C.

In the production of the vinylketene acetals or analogues thereofdescribed above, the product or an intermediate can in each case beisolated and purified in a manner known per se.

The intermediates of the process in accordance with the invention, i.e.the compounds of formulas IV' and IV", are novel compounds and representa further aspect of the present invention.

These novel compounds of formulas IV' and IV" include:

15-Methoxy-15,15'-dihydro-12'-β-carotenoic acid ethyl ester,

15-methoxy-15,15'-dihydro-12'-apocarotenoic acid methyl ester,

12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid ethyl ester,

12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid methyl ester,

12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid 2-hydroxyethylester,

8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid ethyl ester,

8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid methyl ester,

4'-methoxy-β,ψ-caroten-16'-oic acid ethyl ester,

4'-methoxy-β,ψ-caroten-16'-oic acid methyl ester,

12'-methoxy-11,12'-dihydro-8'-apo-β-caroten-8'-oic acid,

11,12,11',12'-tetrahydro-12,12'-dimethoxy-8,8'-diapocarotene-8,8'-dioicacid ethyl ester,

11,12,11',12'-tetrahydro-12,12'-dimethoxy-8,8'-diapocarotene-8,8'-dioicacid methyl ester,

7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidethyl ester and

7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidmethyl ester.

Certain of the novel starting materials (vinylketene acetals andanalogues thereof) of formula III used for the production of the aboveintermediates of formulas IV' and IV" and ultimately of the polyeneesters and acids of formulas I' and I" represent a further aspect of thepresent invention. These novel starting materials in accordance with theinvention are the compounds of the previously given formula IIIa withthe exception of 1,1-dimethoxy-1,3-butadiene and1,1-diethoxy-3-methyl-1,3-butadiene and those of the also previouslygiven formula IIIb with the exception of 2-allylidene- 1,3!dioxolane,2-(1-methyl-allylidene)- 1,3!dioxolane and 2-(2-methyl-allylidene)-1,3!dioxolane. These novel compounds include:

1,1-Dimethoxy-2-methyl-1,3-butadiene,

1,1-dimethoxy-3-methyl-1,3-butadiene,

1,1-diethoxy-1,3-butadiene,

1,1-diethoxy-2-methyl-1,3-butadiene,

2-(1,2-dimethyl-allylidene)- 1,3!dioxolane and

2-(1-methyl-allylidene)- 1,3!dioxane.

The final products of the process in accordance with the invention, i.e.the polyene esters and acids of formulas I' and I", belong for the mostpart to the carotenoid field and can be used appropriately, for exampleas colorants or pigments for foodstuffs, egg yolk, the integuments(especially skin, legs and beak) and/or the subcutaneous fat of poultry,the flesh and/or the integuments (especially skin, scales and shell) offish and crustaceans etc. This use can be effected according to methodsknown per se, as described, for example, in European Patent PublicationNo. 0 630 578.

The use of the novel final products represents a further aspect of thepresent invention.

The invention is illustrated on the basis of the following Examples.

A. Production of Polyene (di)O,O-dialkyl Acetals (Compounds of FormulasII' and II") EXAMPLE 1 15-Apo-β-Carotenal Dimethyl Acetal (Vitamin AAldehyde Dimethyl Acetal)

2.84 g (10 mmol) of vitamin A aldehyde (>99% pure) were placed in 30 mlof methanol and 11 ml (100 mmol, 10 eq.) of trimethyl orthoformate in a100 ml four-necked sulphonation flask equipped with a magnetic stirrer,argon gasification and a thermometer. 40 mg (0.3 mmol, 3 mol %) ofanhydrous zinc chloride were added thereto at 0° C. and the mixture wasstirred at 0° C. for 31/2 hours. Then it was cooled to -40° C. withinone hour and filtered, and the solid was washed with a small amount ofcold (at about -10° C.) methanol and finally dried. This gave 2.5 g (75%yield) of (all-E)-vitamin A aldehyde dimethyl acetal with m.p. 53°-56°C.; content according to HPLC: 98.4%.

For analysis, a sample was recrystallized from methanol. This sampleshowed the following physical and analytical data: m.p. 53°-55° C.;content according to HPLC: 99.7%; UV (n-hexane): 324 nm (log ε=4.70;E=1520).

Microanalysis: Calc.: C 79.95% H 10.37% Found: C 79.66% H 10.50%

EXAMPLE 2 12'-Apo-β-Carotenal Dimethyl Acetal

50 g (0.14 mol) of 12'-apo-β-carotenal and 31 ml (30.1 g, 0.28 mol) offreshly distilled trimethyl orthoformate in 500 ml of methanol wereplaced in a 1.5 l four-necked sulphonation flask equipped with amechanical stirrer, argon gasification and a thermometer. A solution of16 mg of p-toluenesulphonic acid monohydrate in 4 ml of methanol wasthen added at room temperature to the resulting suspension. Thereby, thered crystals dissolved for the most part within 20 minutes; subsequentlyan orange precipitate began to form. After stirring at room temperaturefor 2 hours the mixture was cooled to about +5° C., 0.5 ml oftriethylamine was added, the mixture was stirred at 0° C. for 15minutes, suction filtered (pressure suction filter, under argon), andthe solid washed with a small amount of cold (-10° C.) methanol anddried at room temperature for about 16 hours under reduced pressure(water-jet vacuum). This gave 52.3 g (90.5% yield) of12'-apo-β-carotenal dimethyl acetal as an orange powder with m.p.77°-78° C.; content according to HPLC: 97.5% (very acid-labile); UV(n-hexane): 393 nm (log ε=4.91; E=2045), 376 nm (log ε=4.91; E=2045).

Microanalysis: Calc.: C 81.77% H 10.17% Found: C 81.50% H 9.84%

EXAMPLE 3 8'-Apo-β-Carotenal Dimethyl Acetal

6.25 g (15 mmol) of 8'-apo-β-carotenal and 6.6 ml (6.4 g, 60 mmol, 4eq.) of trimethyl orthoformate in 200 ml of methanol were placed in a350 ml four-necked sulphonation flask equipped with a mechanicalstirrer, argon gasification and a thermometer. A solution of 20 mg ofp-toluenesulphonic acid monohydrate in 10 ml of methanol was addedthereto at room temperature and the mixture was stirred for 21/2 hours.Thereby, the red crystals dissolved slowly and an orange crystallizatebegan to form. Then 2 ml of triethylamine were added, the mixture wascooled to 0° C. within about 30 minutes and suction filtered, and thesolid was washed with a small amount of cold (-10° C.) methanol anddried briefly under reduced pressure (water-jet vacuum). After 30minutes this gave 11.6 g of methanol-moist acetal with a content of94.8% according to HPLC. For recrystallization, the crystals weredissolved in 200 ml of diethyl ether and then 600 ml of methanol wereadded thereto within 11/2 hours, the mixture was cooled to 0° C. and thecrystals were filtered off and dried at room temperature under reducedpressure (water-jet vacuum) and briefly under a high vacuum. This gave5.9 g (84% yield) of 8'-apo-β-carotenal dimethyl acetal as rust-redcrystals with m.p. 131°-132° C.; content according to HPLC: 98.4%; UV(n-hexane): 450 nm (log ε=5.06; E=2476), 424 nm (log ε=5.07; E=2543).

Microanalysis: Calc.: C 83.06% H 10.02% Found: C 82.91% H 10.13%

EXAMPLE 4 4'-Apo-β-Carotenal Dimethyl Acetal

10 g (20.7 mmol) 4'-apo-β-carotenal and 35 ml (0.31 mol, about 15 eq.)of trimethyl orthoformate in 250 ml of methanol were placed in a 500 mlfour-necked sulphonation flask equipped with a mechanical stirrer, argongasification and a thermometer. A solution of 25 mg ofp-toluenesulphonic acid monohydrate in 15 ml of methanol was added atroom temperature to the resulting dark red suspension, the mixture wasstirred at room temperature for 45 minutes, then at 30°-35° C. for 11/2hours; the dark red suspension changed to a brown suspension.Subsequently, 2 ml of triethylamine were added and the mixture wascooled to 0° C. The precipitated crude product was filtered off undersuction, washed with a small amount of cold methanol and dried brieflyat room temperature under reduced pressure. The thus-obtainedmethanol-moist product (about 17.8 g; content according to HPLC: 91%)was dissolved in 600 ml of diethyl ether with slight warming and treatedat room temperature within 1 hour with 1 l of methanol (containing 2%otriethylamine). Then the mixture was suction filtered and the residuewas washed with a small amount of cold (0° C.) methanol. This gave,after drying at room temperature and under reduced pressure for 2 hours,9.3 g (80.5% yield) of 4'-apo-β-carotenal dimethyl acetal as violetcrystals with a content of 94.7% according to HPLC.

For the analytical data, a sample was recrystallized from diethyl ether(dissolved while warming and cooled to 0° C.): content according toHPLC: 95.7%; m.p. 186°-188° C.; UV (dioxan): 500 nm (log ε=4.93;E=1623), 468 nm (log ε=4.99; E=1837), 283 nm (log ε=4.37; E=444).

EXAMPLE 5 12,12'-Diapocarotenal Dimethyl Acetal (C₁₀ -DialdehydeDimethyl Acetal)

32.8 g (0.2 mol) of C₁₀ -dialdehyde and 65 g of trimethyl orthoformatein 250 ml of methanol were placed in a 500 ml round flask equipped witha magnetic stirrer and argon gasification. 100 mg of p-toluenesulphonicacid monohydrate were added thereto at about 20° C., which produced aslightly exothermic reaction. The reaction mixture was held at about20°-25° C. using a cold water bath. The suspension dissolved in about 5minutes. Then the mixture was stirred at room temperature for one hourand about 0.5 ml of triethylamine was subsequently added. The mixturewas concentrated under reduced pressure and the separated crystal slurrywas dissolved in 200 ml of hot n-hexane, filtered while hot throughcotton wool and left to stand. The solution was left to stand at -20° C.in a deep freezer for about 16 hours, the resulting crystals werefiltered off, washed with n-hexane at -20° C. and dried to constantweight under a water-jet vacuum. This gave 42.7 g (80% yield) of C₁₀-dialdehyde dimethyl acetal as pale yellow crystals with m.p. 68°-69° C.and a content according to gas chromatography (GC) of about 96%); UV(ethanol): 292 nm (log ε=4.61; E=1602), 280 nm (log ε=4.72; E=2046), 260nm (log ε=4.59; E=1508).

Microanalysis: Calc.: C 65.60% H 9.44% Found: C 65.43% H 9.14%

EXAMPLE 6 8,8'-Diapocarotenal Dimethyl Acetal (Crocetin DialdehydeDimethyl Acetal)

20.0 g (67.5 mmol) of crocetin dialdehyde (m.p. 196°-197° C.) and 40 g(0.37 mol) of trimethyl orthoformate in 350 ml of methanol were placedin a 500 ml round flask equipped with a magnetic stirrer and argongasification. 200 mg of p-toluenesulphonic acid monohydrate were addedthereto at room temperature while stirring and the mixture was stirredat room temperature for about 45 minutes and at 35°-40° C. for about11/2 hours, which gave a yellow-orange suspension. Then the mixture wascooled to 0° C., filtered and the residue was washed with cold methanol(-10° C.). This gave 24.7 g (92% yield) of crocetin dialdehyde dimethylacetal as an orange powder, m.p. 136° C., with a content of 97.4%according to HPLC. Recrystallization from 150 ml of hot ethyl acetateand 150 ml of methanol while cooling to -20° C. gave, after filtrationand drying (water-jet vacuum, followed by high vacuum), 23.3 g (86%yield) of crocetin dialdehyde dimethyl acetal as rust-red crystals, m.p.138°-139° C., with a content of 97.3% according to HPLC; UV (ethanol):422 nm (log ε=5.12; E=3416), 397 nm (log ε=5.11; E=3305), 377 nm (logε=4.89; E=1985), 232 nm (log ε=4.20; E=405).

Microanalysis: Calc.: C 74.19% H 9.34% Found: C 74.10% H 9.47%

B. Production of vinylketene acetals or analogues thereof (compounds offormula III)

EXAMPLE 7 1,1-Dimethoxy-2-Methyl-1,3-Butadiene Three Steps a), b) andc)!

a) 2-Methyl-3-buteniminoic acid methyl ester hydrochloride

173 g (220 ml, 5.4 mol, 1.1 eq.) of methanol in 2.5 l of toluene and 2.5l of n-hexane were placed in a 6 l four-necked sulphonation flaskequipped with a mechanical stirrer, a thermometer and a gas inlet tube(for argon gasification). 216 g (5.92 mol, 1.2 eq.) of gaseous hydrogenchloride (dried over concentrated sulphuric acid) were introduced at 0°C. (bath temperature -10° C.) and while stirring within 11/2 hours. Then500 g (4.9 mol, 1 eq.) of 80% 2-methyl-3-butenenitrile were addedthereto at between 0° and 5° C. within 45 minutes, the ice bath wasreplaced by a cool (20° C.) water bath and the mixture was stirredfurther at room temperature for about 20 hours. The separatedprecipitate was cooled (ice bath) for 1 hour, filtered off undersuction, washed with 1 l of n-hexane and dried at room temperature for18 hours under reduced pressure (water-jet vacuum). This gave 594 g (81%yield) of 2-methyl-3-buteniminoic acid methyl ester hydrochloride withm.p. 106° C. (with decomposition).

b) 2-Methyl-3-butenoic acid orthomethyl ester

297 g (2 mol) of 2-methyl-3-buteniminoic acid methyl ester hydrochloridewere dissolved at room temperature in 1 l of methanol in aKutscher-Steudel apparatus (2.5 l content, 1 l round flask for pentanecollection). This solution was then extracted continuously with 2 l ofn-pentane over about 24 hours, with the methanol phase being stirredmagnetically. Thereby, ammonium chloride separated. Subsequently, thepentane in the round flask (about 600-700 ml) was concentrated. Thisgave 234 g of crude 2-methyl-3-butenoic acid orthomethyl ester with acontent of 66% according to GC.

A repetition of this procedure on the same scale gave 236 g of crudeproduct with a content of 70% according to GC. The two crude productswere combined (total 470 g) and fractionated at 30 mbar on a Vigreuxcolumn (20 cm, metallized). 310 g (43% yield) of 2-methyl-3-butenoicacid orthomethyl ester with a content of 89.5% according to GC wereobtained at a boiling temperature of 65°-66° C./30 mbar.

c) 1,1-Dimethoxy-2-methyl-1,3-butadiene

About 600 ml of liquid ammonia were condensed at -70° C. using anascending tube in a 1.5 l four-necked sulphonation flask equipped with amechanical stirrer, a thermometer, a dropping funnel and argongasification. 1 spatula tip of iron(III) nitrate was added to thecondensate. Thereafter, 21 g (0.91 mol, 3.2 eq.) of sodium metal wereadded within 30 minutes and the mixture was stirred at -45° to -65° C.,which gave a dark grey suspension. A solution of 50.8 g (0.284 mol) of2-methyl-3-butenoic acid orthomethyl ester with a content of 89.5%according to GC in 200 ml of diethyl ether was then added dropwise at-45° to -40° C. within 1 hour, and the mixture was subsequently stirredat -45° C./1 hour. Thereafter, the cooling was removed and the ammoniawas evaporated within 2 hours (water bath/20° C.). After the addition of200 ml of diethyl ether 100 ml of water were cautiously added dropwiseat between 0° and 20° C., the aqueous phase was separated and againextracted twice with two 150 ml portions, a total of 300 ml, ofn-pentane. After the addition of 40 mg of 2,6-di-tert.butyl-p-cresol thecombined extracts were dried over anhydrous sodium sulphate andconcentrated cautiously at 25°-30° C. under reduced pressure. This gave37.3 g of crude 1,1-dimethoxy-2-methyl-1,3-butadiene with a content of95% according to GC. Distillation on a 10 cm Vigreux column at 20 mbargave, at a boiling temperature of 48° C., 34.2 g (90.2% yield) of1,1-dimethoxy-2-methyl-1,3-butadiene with a content of 96% according toGC as a colourless liquid, which, after the addition of 35 mg (1%o) of2,6-di-tert.butyl-p-cresol, was stored at 0° C. under argon.

EXAMPLE 8 (E/Z)-1-Trimethylsilyloxy-1-Ethoxy-2-Methyl-1,3-Butadiene

25.6 ml (181 mmol, 1,1 eq.) of diisopropylamine in 160 ml oftetrahydrofuran (distilled over LiAlH₄) were placed in a 500 mlfour-necked sulphonation flask equipped with a mechanical stirrer, athermometer, two dropping funnels and argon gasification. 113 ml (181mmol, 1.1 eq.) of a butyllithium solution (1.6M in n-hexane) were addeddropwise thereto at -25° C. within 45 minutes, the mixture was thencooled to -70° C. and a solution of 21.2 g (165 mmol) of ethyl2-methyl-3-butenoate see German Offenlegungsschrift 3,244,273 as well asU.S. Pat. No. 4,937,308! with a content of 100% according to GC in 30 mlof absolute tetrahydrofuran (distilled over LiAlH₄) was added dropwisethereto within 30 minutes. Then the mixture was stirred for 20 minutesat -70° C. and subsequently at this temperature 25.1 ml (=21.6 g, 0.199mol, 1.2 eq.) of trimethylchlorosilane were added dropwise thereto. Thecooling bath was now removed, so that the temperature rose from -70° C.to room temperature within about 21/2 hours. Then the mixture wassuction filtered over Celite® (a filter aid consisting of kieselguhr;Manville Corp., USA), rinsed with tetrahydrofuran, a small amount (about100 mg) of 2,6-di-tert.butyl-p-cresol was added and the mixture wasconcentrated cautiously at 40° C. under reduced pressure. The residuewas taken up in n-pentane and the solution was filtered andconcentrated. Distillation under a high vacuum (0.25 mbar) gave, at aboiling temperature of 28° C. (while cooling well), 25.8 g (73% yield)of (E/Z)-1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene with acontent of 94% according to GC.

EXAMPLE 9 2-(1-Methyl-Allylidene)- 1,3!Dioxolane Two Steps a) and b)!

a) 2-Methyl-but-3-enoic acid 2-chloroethyl ester

45.1 g (0.45 mol) of 2-methyl-3-butenoic acid, 45.33 g (0.56 mol) of2-chloroethanol and 4.1 g (34 mmol) of dimethyl-aminopyridine wereplaced in 450 ml of diethyl ether under argon. 102.2 g (0.495 mol) ofN,N-dicyclohexylcarbodiimide were added thereto in 5 portions at 0° C.within 30 minutes, the mixture was stirred at room temperature for afurther 2 hours and the separated urea was filtered off. The filtratewas washed in succession with 200 ml of 0.5N aqueous hydrochloric acid,100 ml of saturated sodium bicarbonate solution and 100 ml of saturatedsodium chloride solution. The organic solution was dried over anhydrous2 0 sodium sulphate and, after concentration, the product was distilledon a Vigreux column (20 cm) at 80°-81° C./10 mbar. This gave 62.3 g (83%yield) of 2-methyl-but-3-enoic acid 2-chloroethyl ester as a colourlessoil with a content of 97.5% according to GC.

b) 2-(1-Methyl-allylidene)- 1,3!dioxolane

90.6 g (about 113 ml) of 20% potassium hydride in oil (density about0.8) were washed twice with n-hexane under argon, and then treated with700 ml of dimethoxyethane. Subsequently, a solution of 56.5 g (0.34 mol)of 2-methyl-but-3-enoic acid 2-chloroethyl ester with a content of 97.5%according to GC in 175 ml of dimethoxyethane was added thereto whilestirring at 20° C. within 11/2 hours, and the mixture was stirred atroom temperature for 1 hour. 250 ml of water were cautiously addeddropwise thereto at 0°-5° C. The aqueous phase was then separated andextracted three times with three 300 ml portions, a total of 900 ml, ofn-hexane. Washing of the combined organic phases with 250 ml ofsaturated sodium chloride solution, drying and concentration gave ayellow liquid (50.5 g; GC: 83.4%), which, after the addition of 40 mg of2,6-di-tert.butyl-p-cresol, was fractionated on a Vigreux column (20cm). This gave, at a boiling temperature of 93°-94° C./19 mbar, 28.22 g(66% yield) of 2-(1-methyl-allylidene)- 1,3!dioxolane as a colourlessoil with a content of 100% according to GC.

C. Production of the compounds of formulas IV' and IV" from the polyene(di)O,O-dialkyl acetals of formula II' and II", respectively, and thevinylketene acetals or analogues thereof of formula III

EXAMPLE 10 15-Methoxy-15,15'-Dihydro-12'-β-Carotenoic Acid Ethyl Ester

1.75 g (5 mmol) of vitamin A aldehyde dimethyl acetal (HPLC: 98%) and1.5 g (6.5 mmol) of(E/Z)-1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (GC: 87%) in20 ml of tert.butyl methyl ether were placed in a 50 ml four-neckedsulphonation flask equipped with a thermometer, a magnetic stirrer andargon gasification. 7 drops (=about 80 mg, 10 mol %) of borontrifluoride etherate were added thereto at -30° C. within 20 minutes.After 1 hour tlc (SiO₂): R_(f) =about 0.3; cyclohexane/ethyl acetate(9:1)! 1 ml of triethylamine was added at -30° C. and the mixture waswarmed to room temperature and poured into 20 ml of water. The separatedaqueous phase was extracted twice with 20 ml portions, a total of 40 ml,of n-hexane and the combined organic phases were washed with 20 ml ofsaturated sodium chloride solution, dried over anhydrous sodium sulphateand concentrated. Chromatographic purification of the yellow, oily crudeproduct (2.7 g) on 100 g of silica gel (0.04-0.063 mm) withcyclohexane/ethyl acetate (9:1) gave 1.68 g (74% yield) of15-methoxy-15,15'-dihydro-12'-β-carotenoic acid ethyl ester as a thickyellow oil (content according to HPLC: 97%); UV (n-hexane): 325 nm (logε=4.63; E=989).

EXAMPLE 11 15-Methoxy-15,15'-Dihydro-12'-Apocarotenoic Acid Methyl Ester

1.75 g (5 mmol) of vitamin A aldehyde dimethyl acetal (HPLC: 98%) and0.8 g (6.5 mmol, 1,3 eq.) of 1,1-dimethoxy-2-methyl-1,3-butadiene (GC:99%) in 20 ml of tert.butyl methyl ether were placed in a 50 ml flaskunder argon. 5 drops (about 60 mg, 8 mol %) of boron trifluorideetherate were added thereto while stirring at -30° C. and the mixturewas stirred further at about -30° C. (initially a very dark colouredsolution, which lightened to an orange solution after about 10 minutes:tlc (SiO₂): R_(f) =about 0.3; n-hexane/ethyl acetate=9:1).

For the hydrolysis, 5 ml of acetic acid/water (9:1) were then added at-30° C. and the mixture was stirred at 0° C. for 20 minutes. Then 20 mlof water were added, the mixture was extracted with two 20 ml portions,a total of 40 ml, of n-hexane and the combined organic phases werewashed once with 20 ml of saturated sodium bicarbonate solution and oncewith sodium chloride solution, dried over anhydrous sodium sulphate andconcentrated under reduced pressure. The crude product (2.5 g) waschromatographed on 125 g of silica gel (0.040-0.063 mm) withn-hexane/ethyl acetate (9:1). This gave 1.50 g (69% yield) of15-methoxy-15,15'-dihydro-12'-apocarotenoic acid methyl ester as ayellow oil; content according to HPLC: 95.2%; UV (n-hexane): 325 nm (logε=4.67; E=1132).

Microanalysis: Calc.: C 78.60% H 9.77% Found: C 78.26% H 10.08%

In this chromatography there could be isolated in an early fraction 130mg (about 6%) of (13-cis)-15-methoxy-15,15'-dihydro-12'-apocarotenoicacid methyl ester as a yellow oil; content according to HPLC: 95.3%; UV(n-hexane): 329 nm (log ε=4.58; E=926).

EXAMPLE 12 12'-Methoxy-11',12'-Dihydro-8'-Apo-β-Carotenoic Acid EthylEster

495 mg (1.25 mmol) of 12'-apo-β-carotenal dimethyl acetal and 325 mg(1.5 mmol) of (E/Z)-1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene(GC: 92%) in 5 ml of tert.butyl methyl ether were placed in a 10 mlround flask under argon. 17 mg (10 mol %) of anhydrous zinc chloridewere added thereto at 0° C. and the mixture was stirred at +5° C. for 2hours tlc(SiO₂): R_(f) =about 0.2; toluene!. The orange-red reactionmixture was poured into 20 ml of water and extracted with two 20 mlportions, a total of 40 ml, of n-hexane, dried over anhydrous sodiumsulphate and concentrated under reduced pressure. The crude product (760mg) was chromatographed on 30 g of silica gel (0.040-0.063 mm) withtoluene. This gave 609 mg (93% yield) of(all-E)-12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid ethyl esteras a viscous orange oil; content according to HPLC: 94%. Thespectroscopic data came from an analogous batch: UV (n-hexane): 395 nm(log ε=4.81; E=1300), 376 nm (log ε=4.82; E=1339).

Microanalysis: Calc.: C 80.44% H 9.82% Found: C 80.49% H 10.15%

EXAMPLE 13 12'-Methoxy-11',12'-Dihydro-8'-Apo-β-Carotenoic Acid MethylEster

6.2 g (15 mmol) of 12'-apo-β-carotenal dimethyl acetal and 3.1 g (24mmol, 1.6 eq.) of 1,1-dimethoxy-2-methyl-1,3-butadiene (GC: 100%) in 60ml of tert.butyl methyl ether were placed at -25° C. under argon in a100 ml round flask. 80 mg (about. 6 drops, 4 mol %) of boron trifluorideetherate were added thereto at -25° C. while stirring and the mixturewas stirred at -25° C. for 1 hour tlc (SiO₂): R_(f) =about 0.25;toluene!. Then 15 ml of acetic acid/water (9:1) were added thereto andthe mixture was stirred at room temperature for 30 minutes. Then themixture was poured into 100 ml of tert.butyl methyl ether, washed withfour 100 ml portions, a total of 400 ml, of water and the aqueous phaseswere extracted with 100 ml of tert.butyl methyl ether. The organicphases were combined, washed with 100 ml of saturated sodium bicarbonatesolution and 100 ml of saturated sodium chloride solution, dried overanhydrous sodium sulphate, filtered and evaporated under reducedpressure. The separated dark oil (9.2 g) was chromatographed on 250 g ofsilica gel (0.040-0.063 mm) with toluene/ethyl acetate (19:1). This gave6.9 g (89% yield) of 12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoicacid methyl ester as a red-orange, viscous oil with a content of 93.1%according to HPLC. UV (cyclohexane with 3% chloroform): 398 nm (logε=4.77; E=1225), 380 nm (log ε=4.78; E=1257).

Microanalysis: Calc.: C 80.29% H 9.69% Found: C 80.45% H 9.53%

EXAMPLE 14 12'-Methoxy-11,12'-Dihydro-8'-Apo-β-Carotenoic Acid2-Hydroxyethyl Ester

2.98 g (7.3 mmol) of 12'-apo-β-carotenal dimethyl acetal (contentaccording to HPLC: about 97%) and 1.42 g (11.25 mmol) of2-(1-methyl-allylidene)- 1,3!dioxolane (GC: 100%) in 30 ml of tert.butylmethyl ether were placed in a 100 ml round flask while gassing withargon. 2 drops (about 25 mg, 2 mol %) of boron trifluoride etherate wereadded thereto while stirring at -25° C. and the mixture was stirred atthis temperature for 1 hour. Then 8 ml of acetic acid/water (9:1) wereadded thereto, the cooling was removed and the mixture was left to warmto room temperature within 30 minutes R_(f) =about 0.4, n-hexane/ethylacetate 1:1). The reaction mixture was then poured into 100 ml oftert.butyl methyl ether and washed twice with 150 ml of water each time,once with 100 ml of saturated sodium bicarbonate solution and once with50 ml of saturated sodium chloride solution. Subsequently, the organicphase was dried over anhydrous sodium sulphate, filtered andconcentrated, and the crude product (4.1 g) was chromatographed on 120 gof silica gel (0.040-0.063 mm) with n-hexane/ethyl acetate (1:1) Aftercrystallization from n-hexane there were obtained 1.85 g (49%) of12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid 2-hydroxyethylester as pale yellow crystals, m.p. 98°-100° C., with a content of 97.6%according to HPLC. UV (n-hexane): 395 nm (log ε=4.92; E=1634), 377 nm(log ε=4.93; E=1669).

A resinous byproduct (65 mg), presumably having the following structure(according to ¹ H-NMR and mass spectrum) could be isolated from themother liquor of the crystallization after chromatography on silica gel(eluent: toluene/ethyl acetate=8:2): ##STR22##

EXAMPLE 15 8'-Methoxy-7',8'-Dihydro-4'-Apo-β-Carotenoic Acid Ethyl Ester

4.73 g (10 mmol) of 8'-apo-β-carotenal dimethyl acetal (contentaccording to HPLC: 98%) and 2.56 g (12 mmol, 1,2 eq.) of(E/Z)-1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (GC: 94%) in100 ml of tert.butyl methyl ether were placed in a 250 ml found flaskwhile gassing with argon. 66 mg (0.5 mmol, 5 mol %) of anhydrous zincchloride were added thereto at 0° C. and the mixture was stirred at roomtemperature for 3 hours tlc (SiO₂): R_(f) =about 0.2; toluene!. Then 50ml of water were added and, after separation, this was extracted with 50ml of n-hexane. After drying over anhydrous sodium sulphate, filtrationand evaporation of the solvent the separated red oil (5 g) was dissolvedin 100 ml of ethanol while heating and slowly cooled to 0° C. Theseparated crystals were filtered off under suction, washed with a smallamount of cold ethanol and dried at room temperature under a water-jetvacuum. This gave 3.8 g (65% yield) of8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid ethyl ester as redcrystals with m.p. 107°-108° C.; content according to HPLC: 96.4%; UV(n-hexane): 451 nm (log ε=5.04; E=1955), 425 nm (log ε=5.08; E=2146).

EXAMPLE 16 8'-Methoxy-7',8'-Dihydro-4'-Apo-β-Carotenoic Acid MethylEster

4.80 g (10 mmol) of 8'-apo-β-carotenal dimethyl acetal (contentaccording to HPLC: 97%) and 2.20 g (17 mmol) of1,1-dimethoxy-2-methyl-1,3-butadiene (GC: 99%) in 100 ml of tert.butylmethyl ether were placed in a 50 ml round flask while gassing withargon. One drop (12 mg) and then after 30 minutes a further one drop, atotal of two drops (24 mg, about 2 mol %), of boron trifluoride etheratewere added thereto at 0° C. while stirring and the mixture was stirredat 0° C. for 1 hour in total.

For the hydrolysis, 20 ml of acetic acid/water (9:1) were added at 0° C.to the mixture, which was stirred at room temperature for about 50minutes tlc (SiO₂): R_(f) =about 0.2; toluene!. Then the solution wasplaced in a separating funnel and washed with two 100 ml portions, atotal of 200 ml, of water and 100 ml of saturated sodium bicarbonatesolution. The aqueous phases were each extracted with 100 ml ofn-hexane. Drying over anhydrous sodium sulphate, filtration andevaporation under reduced pressure gave 8.6 g of a thick oil, which wasdissolved in 250 ml of ethanol while warming slightly. After cooling to0° to -20° C., filtration and drying of the crystals there were obtained3.0 g (53% yield) of 8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acidmethyl ester as orange crystals, m.p. 84°-86° C., with a content of96.2% according to HPLC. UV (cyclohexane with 3% chloroform): 456 nm(log ε=4.77; E=1087), 430 nm (log ε=4.82; E=1225), 407 nm (log ε=4.67;E=855).

EXAMPLE 17

Isolation/characterization of the orthoester8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid orthomethyl esteroccurring as the intermediate (see Example 16: acid-catalyzed hydrolysisomitted) ##STR23##

4.60 g (9.6 mmol) of 8'-apo-β-carotenal dimethyl acetal (contentaccording to HPLC: 97%) and 1.95 g (15 mmol) of1,1-dimethoxy-2-methyl-1,3-butadiene (GC: 99%) in 75 ml of tert.butylmethyl ether were placed in a 150 ml round flask while gassing withargon. One drop (12 mg, about 1 mol %) of boron trifluoride etherate wasadded at 0° C. below the reaction suspension. After a short time a darkred reaction solution formed, from which orange crystals separated.Stirring at 0° C. for ten minutes, suction filtration, washing of thesolid with a small amount of a cold methanol/water (9:1) mixture anddrying under a water-jet vacuum and subsequently under a high vacuum atroom temperature gave 3.50 g (61% yield) of8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid orthomethyl ester asorange crystals, m.p. 131°-132° C. UV (cyclohexane with 3% chloroform):456 nm (log ε=5.04; E=1855), 430 nm (log ε=5.08; E=2047), 410 nm (logε=4.91; E=1362).

Microanalysis: Calc.: C 79.28% H 9.89% Found: C 79.09% H 9.86%

EXAMPLE 18 4'-Methoxy-β,ψ-Caroten-16'-Oic Acid Ethyl Ester

2.91 g (5 mmol) of 4'-apo-β-carotenal dimethyl acetal (content accordingto HPLC: 91%) and 1.21 g (6 mmol) of1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (GC: 99%) in 50 mlof tert.butyl methyl ether were placed in a 150 ml round flask equippedwith a magnetic stirrer and argon gasification and treated at 0° C. with70 mg (0.5 mmol, 10 mol %) of anhydrous zinc chloride. Then the mixturewas stirred at room temperature for about 18 hours tlc (SiO₂): R_(f)=about 0.2; toluene!, poured into water and worked-up as usual (seeExample 10). This gave a dark red, viscous residue (5.4 g), which waschromatographed on 250 g of silica gel (0.04-0.063 mm) with toluene. Aglutinous product (1.9 g, content according to HPLC: about 70%) wasobtained. This residue was digested once in 40 ml of ethanol and once in25 ml of hot (50° C.) ethanol, cooled (0° C.) and dried. This gave 0.86g (26% yield) of 4'- methoxy-β,ψ-caroten-16'-oic acid ethyl ester asdark red crystals with m.p. 124°-125° C. and a content of 95.4%according to HPLC. UV (cyclohexane with 3% chloroform): 496 nm (logε=4.98; E=1530), 464 nm (log ε=5.05; E=1790), 439 nm (log ε=4.91;E=1290).

EXAMPLE 19 4'-Methoxy-β,ψ-Caroten-16'-Oic Methyl Ester

2.91 g (5 mmol) of 4'-apo-β-carotenal dimethyl acetal (content accordingto HPLC: 91%) and 1.10 g (8.5 mmol) of1,1-dimethoxy-2-methyl-1,3-butadiene (GC: 98%) were suspended in 50 mlof tert.butyl methyl ether in a 150 ml flask equipped with a magneticstirrer and argon gasification. One drop (12 mg, 2 mol %) of borontrifluoride etherate was added thereto at 0° C. and the mixture wassubsequently stirred at room temperature for 1 hour. Then 20 ml ofacetic acid/water (9:1) were added and the mixture was stirred at roomtemperature for 2 hours tlc (SiO₂): R_(f) =about 0.2;toluene!. Usualworking-up (see Example 11) and chromatography of the residue on 250 gof silica gel (0.04-0.063 mm) with toluene gave a glutinous, dark redresidue (2.2 g), which was digested in 60 ml of hot ethanol (50° C.).After cooling to 0° C., filtration and drying there was obtained 0.90 g(28% yield) of 4'-methoxy-β,ψ-caroten-16'-oic acid methyl ester as darkred crystals with m.p. 120°-123° C. and a content of 98.0% according toHPLC. UV (cyclohexane with 3% chloroform): 469 nm (log ε=5.10; E=2058),465 nm (log ε=5.16; E=2220), 440 nm (log ε=4.99; E=1610).

EXAMPLE 20 12'-Methoxy-11,12'-Dihydro-8'-Apo-β-Caroten-8'-Oic Acid

2.97 g (7.3 mmol) of 12'-apo-β-carotenal dimethyl acetal (contentaccording to HPLC: about 97%) and 2.63 g (9.7 mmol) of1,1-bis(trimethylsilyloxy)-2-methyl-1,3-butadiene (content according toGC: 90.5%) in 30 ml of tert.butyl methyl ether were placed while gassingwith argon in a 100 ml round flask equipped with a magnetic stirrer. 100mg (0.7 mmol, 10 mol %) of anhydrous zinc chloride were added thereto at0° C. and the mixture was stirred at this temperature for a further 5hours. Then the reaction solution was poured into water, which causedthe immediate hydrolysis of the intermediate of formula V', andextracted as usual (see Example 12). This gave a red resin (4.5 g),which was chromatographed on 200 g of silica gel (0.04-0.063 mm) withtoluene/ethyl acetate (3:1). There were obtained 1.90 g (50% yield) of12'-methoxy-11,12'-dihydro-8'-apo-β-caroten-8'-oic acid as a glutinous,orange-red foam (content after methylation with diazomethane andaccording to HPLC: 88.6%); UV (cyclohexane with 5% chloroform): 398 nm(log ε=4.71; E=1100), 379 nm (log ε=4.72; E=1340).

EXAMPLE 2111,12,11',12'-Tetrahydro-12,12'-Dimethoxy-8,8'-Diapocarotene-8,8'-DioicAcid Ethyl Ester

3.85 g (14.4 mmol) of 12,12'-diapocarotenal dimethyl acetal (m.p.68°-69° C.; GC: 96%) and 7.84 g (36 mmol) of1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (content accordingto GC: 94%) in 60 ml of tert.butyl methyl ether were placed whilegassing with argon in a 100 ml two-necked round flask equipped with athermometer. 100 mg (0.7 mmol, 5 mol %) of anhydrous zinc chloride wereadded thereto at 0° C. and the mixture was stirred at room temperaturefor about 16 hours tlc (SiO₂): R_(f) =about 0.2-0.3; n-hexane/ethylacetate (4:1)!. 200 mg of 2,6-di-tert.butyl-p-cresol and then 25 ml ofwater were added to the yellowish reaction mixture, which was stirred atroom temperature for 5 minutes, and the aqueous phase was separated andextracted twice with 50 ml, a total of 100 ml, of tert.butyl methylether. The combined organic phases were washed with 50 ml of saturatedsodium bicarbonate solution and 50 ml of saturated sodium chloridesolution, dried over anhydrous sodium sulphate and concentrated underreduced pressure. The separated oil (about 10 g) was chromatographed on250 g of silica gel (0.04-0.063 mm) with n-hexane/ethyl acetate (4:1).This gave 6.28 g (93% yield) of11,12,11',12'-tetrahydro-12,12'-dimethoxy-8,8'-diapocarotene-8,8'-dioicacid ethyl ester as a yellow oil (isomer mixture: mixture of twodiastereomeric enantiomer pairs; content according to HPLC: 96.1%); UV(ethanol): 298 nm (log ε=4.61; E=904), 289 nm (log ε=4.72; E=1170), 276nm (log ε=4.59; E876).

Microanalysis: Calc.: C 69.61% H 8.99% Found: C 69.79% H 8.84%

EXAMPLE 2211,12,11',12'-Tetrahydro-12,12'-Dimethoxy-8,8'-Diapocarotene-8,8'-DioicAcid Methyl Ester

3.85 g (14.4 mmol) of 12,12'-diapocarotenal dimethyl acetal (m.p.68°-69° C.; GC: 96%) and 5.37 g (40 mmol, 2.7 eq.) of1,1-dimethoxy-2-methyl-1,3-butadiene (content according to GC: 94.5%) in75 ml of tert.butyl methyl ether were placed in a 100 ml two-neckedround flask equipped with a thermometer. On two occasions 6 drops, atotal of 12 drops (about 140 mg, 7 mol %), of boron trifluoride etheratewere added thereto within one hour at -20° C. and the mixture wasstirred at -20° C. for 2 hours tlc (SiO₂): R_(f) =about 0.2;n-hexane/ethyl acetate (4:1)!. Then 20 ml of acetic acid/water (9:1)were added, the mixture was stirred at 0° C. for 20 minutes, poured into50 ml of water and worked-up analogously to Example 21. The separatedyellow oil (7.1 g) was chromatographed on 250 g of silica gel(0.04-0.063 mm) with n-hexane/ethyl acetate (4:1). This gave 5.15 g (85%yield) of11,12,11',12'-tetrahydro-12,12'-dimethoxy-8,8'-diapocarotene-8,8'-dioicacid methyl ester (mixture of two diastereomeric enantiomer pairs) as ayellow oil; content according to HPLC: 99.6%. A sample crystallized fromn-hexane was used for the analysis: m.p. 68°-71° C.; content accordingto HPLC: 99.7%; UV (chloroform): 301 nm (log ε=4.58; E=901), 289 nm (logε=4.69; E=1157).

Microanalysis: Calc.: C 68.55% H 8.63% Found: C 68.18% H 8.58%

EXAMPLE 237,8,7',8'-Tetrahydro-8,8'-Dimethoxy-4,4'-Diapocarotene-4,4'-Dioic AcidEthyl Ester

2.54 g (7.5 mmol) of crocetin dialdehyde dimethyl acetal (contentaccording to HPLC: 97.3%) and 4.79 g (22.5 mmol, 3 eq.) of1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (GC: 94%) in 60 mlof tert.butyl methyl ether were placed in a 150 ml round flask whilegassing with argon. 105 mg (0.75 mmol, 10 mol %) of anhydrous zincchloride were added thereto at 0° C. and the mixture was stirred at roomtemperature for about 16 hours tlc (SiO₂): R_(f) =about 0.3;cyclohexane/ethyl acetate (4:1)!. Working-up was effected analogously toExample 21 and, after evaporation of the solvent, gave 3.83 g of crude7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidethyl ester (mixture of two diastereomeric enantiomer pairs) as anorange oil. For purification, this crude product was dissolved in 10 mlof hot methanol and crystallized out at 0° C. for about 16 hours. Thisgave 2.20 g (49.4% yield) of product (as a mixture of two diastereomericenantiomer pairs) as an orange crystalline powder, m.p. 61°-65° C.;content according to HPLC: 97.8%. Analysis was effected on a productwith m.p. 63°-80° C. which was prepared, chromatographed andcrystallized analogously; content according to HPLC: 98.4%; UV(cyclohexane with 3% chloroform): 428 nm (log ε=5.02; E=1811), 402 nm(log ε=5.01; E=1779), 381 nm (log ε=4.79; E=1074).

EXAMPLE 247,8,7',8'-Tetrahydro-8,8'-Dimethoxy-4,4'-Diapocarotene-4,4'-Dioic AcidMethyl Ester

2.91 g (8.4 mmol) of crocetin dialdehyde dimethyl acetal (contentaccording to HPLC: 97.3%) and 3.92 g (30 mmol, 3 eq.) of1,1-dimethoxy-2-methyl-1,3-butadiene (GC: 98%) in 60 ml of tert.butylmethyl ether were placed while gassing with argon in a 100 ml flaskequipped with a thermometer. At intervals of 10 minutes 4 separate drops(total about 50 mg, 4 mol %) of boron trifluoride etherate were addedthereto at 0° C. After a further 30 minutes at 0° C. a further 2 drops(about 25 mg, 2 mol %) of boron trifluoride etherate were added. After afurther hour at 0° C. 20 ml of acetic acid/water (9:1) were added, themixture was stirred at 0° C. for 20 minutes, poured into 50 ml of waterand worked-up analogously to Example 21 tlc (SiO₂): R_(f) =about 0.3(product); R_(f) =about 0.25 (educt); cyclohexane/ethyl acetate (4:1)!.This gave 6.5 g of crude product, which was chromatographed on 200 g ofsilica gel (0.04-0.063 mm) with n-hexane/ethyl acetate (4:1). There wereobtained 3.05 g of7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidmethyl ester as an orange solid, m.p. 73°-77° C.; content according toHPLC: 84.7%. For further purification, recrystallization was carried outfrom 15 ml of hot ethanol after cooling to 0° to -20° C. This gave 2.4 g(51% yield) of7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidmethyl ester (mixture of two diastereomeric enantiomer pairs) as orangecrystals, m.p. 83°-84° C.; content according to HPLC: 98.7%; UV(cyclohexane with 3% chloroform): 428 nm (log ε=5.05; E=2045), 402 nm(log ε=5.04; E=1996), 381 nm (log ε=4.82; E=1209).

EXAMPLE 25

Isolation/characterization of the bis-orthoester7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidorthomethyl ester occurring as the intermediate (see Example 24:acid-catalyzed hydrolysis excluded) ##STR24##

1.94 g (5.6 mmol) of crocetin dialdehyde dimethyl acetal (contentaccording to HPLC: 97.3%) and 2.0 g (15.5 mmol) of1,1-dimethoxy-2-methyl-1,3-butadiene (GC: 99.5%) in 40 ml of tert.butylmethyl ether were treated at 0° C. in a 100 ml round flask while gassingwith argon with 140 mg (1 mmol) of anhydrous zinc chloride and stirredat room temperature for about 16 hours tlc (SiO₂): R_(f) =about 0.15(product); R_(f) =0.25 (educt); cyclohexane/ethyl acetate (4:1)!. Forthe working-up, the mixture was poured into water and extracted withethyl acetate. This gave, after evaporation under reduced pressure, acrude product (4.8 g), which was dissolved in n-hexane/ethyl acetate(6:1). After cooling to 0° C. a yellow product separated and this wasfiltered off (0.9 g), dissolved in 45 ml of warm methanol and cooled to0° to -20° C. This gave 0.59 g (about 16% yield) of 7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidorthomethyl ester as yellow crystals, m.p. 143°-147° C. Contentaccording to HPLC: 96.8%; UV (cyclohexane with 3% chloroform): 428 nm(log ε=5.09; E=1920), 402 nm (log ε=5.08; E=1864), 381 nm (log ε=4.86;E=1116).

Microanalysis: Calc.: C 70.77% H 9.38% Found: C 70.84% H 8.98%

D. Manufacture of the Polyene Esters or Acids of Formulas I' and I" fromthe Compounds of Formulas IV' and IV", Respectively EXAMPLE 2612'-Apo-β-carotenoic Acid Ethyl Ester

3.80 g (8.75 mmol) of 15-methoxy-15,15'-dihydro-12'-apocarotenoic acidmethyl ester in 15 ml of ethanol were placed in a 150 ml round flaskwhile gassing with argon. A sodium ethylate solution, prepared bydissolving 0.64 g (27 mmol; 3 eq.) of sodium in 35 ml of ethanol, wasadded at room temperature and the mixture was stirred at 40° C. for 2hours, giving a dark brown solution tlc (SiO₂): R_(f) =about 0.5;cyclohexane/ethyl acetate (9:1)!. Then1.2 ml (1.3 g, 21 mmol) of aceticacid were added at room temperature, whereupon a yellow suspensionformed and was cooled to -40° C., stirred for 11/2 hours and the solidwas filtered off under suction. This was washed once with 20 ml ofmethanol at -20° C., twice with 50 ml portions, a total of 100 ml, ofwater at room temperature and once again with 50 ml of methanol at -20°C., and finally dried at 30° C. under a water-jet vacuum and then atroom temperature under a high vacuum. This gave 2.30 g (63% yield) of12'-apo-β-carotenoic acid ethyl ester as an orange powder, m.p. 80°-81°C.; content according to HPLC: 95%; UV (n-hexane): 398 nm (log ε=4.90;E=2028).

Microanalysis: Calc.: C 82.18% H 9.71% Found: C 82.03% H 9.75%

EXAMPLE 27 12'-Apo-β-carotenoic Acid Methyl Ester

1.36 g (3.25 mmol) of 15-methoxy-15,15'-dihydro-12'-apocarotenoic acidmethyl ester in 20 ml of methanol were placed in a 100 ml round flaskwhile gassing with argon. 10 ml (10 mmol) of a 1 molar solution ofsodium methylate in methanol were added thereto at room temperature andthe mixture was stirred at 50° C. for 3 hours, which gave a darkreaction solution tlc (SiO₂): R_(f) =about 0.4-0.5; n-hexane/ethylacetate (9:1)!. Then the mixture was cooled to 0° C. and 1.2 g (20 mmol)of acetic acid were added followed by 20 ml of water, whereupon anorange glutinous precipitation occurred. The suspension was washed with75 ml of ethyl acetate into a separating funnel containing 50 ml ofwater. The aqueous phase was separated and extracted with 75 ml of ethylacetate. After drying over anhydrous sodium sulphate the organic phasewas concentrated under reduced pressure and the residue (1.8 g) waschromatographed on 50 g of silica gel (0.04-0.063 mm) withn-hexane/ethyl acetate (14:1). This gave 1.3 g of an orange oil, whichwas dissolved in 10 ml of ethanol and crystallized at 0° to -20° C. forabout 16 hours. There was obtained 0.55 g (44% yield) of12'-apo-β-carotenoic acid methyl ester as red crystals, m.p. 73°-83° C.;content according to HPLC: 98%. UV (n-hexane): 398 nm (log ε=4.90;E=2100).

Microanalysis: Calc.: C 82.06% H 9.54% Found: C 82.15% H 9.61%

EXAMPLE 28

8'-Apo-β-carotenoic acid ethyl ester (through process from12'-apo-β-carotenal dimethyl acetal and1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene via12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid ethyl ester)

A solution of 12.40 g (30 mmol) of 12'-apo-β-carotenal dimethyl acetal(m.p. 78°-79° C.; HPLC: 96.5%) and 7.6 g (36 mmol, 1.2 eq.) of1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (content accordingto GC: 95%) in 120 ml of tert.butyl methyl ether was treated at 0° C. ina 300 ml round flask equipped with a magnetic stirrer and argongasification with 80 mg (0.6 mmol, 2 mol %) of anhydrous zinc chlorideand stirred at room temperature for about 16 hours tlc (SiO₂): R_(f)(acetal)=about 0.3; R_(f) (product)=about 0.2; toluene!. Then 200 mg of2,6-di-tert.butyl-p-cresol were added and the mixture was added to 50 mlof water. After separating the aqueous phase it was extracted with 50 mlof tert.butyl methyl ether, washed with 50 ml of saturated sodiumbicarbonate solution and 50 ml of saturated sodium chloride solution,dried over anhydrous sodium sulphate, filtered and concentrated underreduced pressure. In order to remove remaining organic solvent andwater, the oily residue was dissolved in 200 ml of absolute ethanol andconcentrated under reduced pressure. This gave 17.4 g of crude12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid ethyl ester as ared-orange sticky, ethanol-moist oil (content according to HPLC: 89.7%).

This oil was placed with 250 ml of absolute ethanol in a 500 mlfour-necked sulphonation flask equipped with a mechanical stirrer, argongasification, a thermometer and a dropping funnel. A sodium ethylatesolution, prepared by dissolving 1.40 g (60 mmol, 2 eq.) of sodium in 70ml of absolute ethanol, was added thereto at room temperature and themixture was stirred at room temperature for about 16 hours. Aprecipitate began to form after about 1-2 hours. In order to completethe reaction, the thick precipitate was stirred at 40° C. for 4 hourstlc (SiO₂): R_(f) =about 0.4; only traces of intermediate; toluene!.Then the mixture was cooled to 25° C. and a solution of 4.2 g (70 mmol)of acetic acid in 10 ml of ethanol was added dropwise followed by amixture of 40 ml of ethanol and 42 ml of water within about 1 hour. Themixture was subsequently cooled to +5° C. with an ice bath and filtered,and the filter material was washed at 0° C. with 50 ml of ethanol/water(9:1) and at room temperature with three 50 ml portions, a total of 150ml, of water and dried at room temperature under a high vacuum for 16hours. This gave 12.50 g of crude 8'-apo-β-carotenoic acid ethyl esteras a brick-red powder with m.p. 136°-137° C.; content according to HPLC:99.1% (all-E).

For further purification, 12.40 g of the above product were suspended in100 ml of acetone and the suspension was refluxed while stirring. Afterrefluxing for a quarter of an hour the product did not pass completelyinto solution. 5 ml of water were added dropwise to the refluxingsuspension through the reflux condenser in about one minute whilestirring, then the mixture was cooled slowly to 0° C., filtered andwashed twice with two 20 ml portions, a total of 40 ml, of coldacetone/water (9:1) and twice with two 25 ml portions, a total of 50 ml,of water at -20° C. After drying at 45° C. under a water-jet vacuum toconstant weight and at room temperature under a high vacuum (0.05 mmHg)there were obtained 11.00 g (80% yield) of 8'-apo-β-carotenoic acidethyl ester as dark red glistening crystals with m.p. 139° C. and acontent according to HPLC of 99.6%. UV (cyclohexane with 3% chloroform):473 nm (log ε=4.98; E=2065), 447 nm (log ε=5.06; E=2481), 262 nm (logε=4.25; E=385).

EXAMPLE 29

8'-Apo-β-carotenoic acid ethyl ester (through process from12'-apo-β-carotenal dimethyl acetal and1,1-dimethoxy-2-methyl-1,3-butadiene via12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid methyl ester)

A solution of 6.20 g (15 mmol) of 12'-apo-β-carotenal dimethyl acetal(m.p. 78°-79° C.; HPLC: 96.5%) and 3.04 g (22.5 mmol) of1,1-dimethoxy-2-methyl-1,3-butadiene (content according to GC: 95%) in60 ml of tert.butyl methyl ether was treated at -25° C. while gassingwith argon in a 100 ml round flask equipped with a magnetic stirrer with80 mg (about 6 drops, about 0.6 mmol, 4 mol %) of boron trifluorideetherate. The colour of the solution changed to deep blue upon additionof the catalyst. The solution was stirred for about one hour tlc (SiO₂):R_(f) about 0.2 (toluene)!. For the hydrolysis, 15 ml of aceticacid/water (9:1) were added at -25° C. and the mixture was warmed to 0°C., stirred at room temperature for about 30 minutes and worked-upanalogously to Example 21. This gave 10.0 g of crude12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid methyl ester as ared, sticky, ethanol-moist oil, which was dissolved in 130 ml of ethanolin a 350 ml four-necked sulphonation flask equipped with a mechanicalstirrer, a thermometer and argon gasification. After the addition of asodium ethylate solution, prepared by dissolving 700 mg (30 mmol) ofsodium in 35 ml of absolute ethanol, the mixture was stirred at roomtemperature for about 16 hours and at 50° C. for 11/2 hours. Working-upwas effected analogously to Example 28. This gave 6.1 g (86%) of8'-apo-β-carotenoic acid ethyl ester as a red-violet powder, m.p. 140°C.; content according to HPLC: 97.5%. Recrystallization in acetone/wateranalogously to Example 28 gave 5.81 g (83% yield) of 8'-apo-β-carotenoicacid ethyl ester as violet, metallic-glistening crystals, m.p. 141° C.;content according to HPLC: 98.3%.

EXAMPLE 30

8'-Apo-β-carotenoic acid ethyl ester (through process from12'-apo-β-carotenal dimethyl acetal and 2-(1-methyl-ethylidene)-1,3!dioxolane via 12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid2-hydroxyethyl ester)

16.4 g (40 mmol) of 12'-apo-β-carotenal dimethyl acetal (contentaccording to HPLC: 96.8%) and 7.57 g (60 mmol) of2-(1-methyl-allylidene)- 1,3!dioxolane (content according to GC: 100%)in 160 ml of ethyl acetate were placed in a 350 ml four-neckedsulphonation flask while gassing with argon. 210 mg (4 mol %) of borontrifluoride etherate were added thereto at -25° C. and the mixture wasstirred at this temperature for 1 hour. Then 40 ml of acetic acid/water(9:1) were added, the cooling was removed and the mixture was stirred atabout 17° C. for a further 40 minutes tlc (SiO₂): R_(f) =about 0.35;n-hexane/ethyl acetate (1:1)!. For the working-up, the reaction mixturewas poured into 500 ml of ethyl acetate, washed with two 400 mlportions, a total of 800 ml, of water, once with 300 ml of saturatedsodium bicarbonate solution and once with 150 ml of saturated sodiumchloride solution. Then, the organic phase was dried over anhydroussodium sulphate and concentrated. The oily residue was evaporated twicewith in each case 250 ml, a total of 500 ml, of ethanol at 35° C. underreduced pressure. This gave a viscous orange-red oil (24 g), which wasdissolved in 350 ml of ethanol and treated at room temperature in a 750ml four-necked sulphonation flask equipped with a mechanical stirrer andwhile gassing with argon with a sodium ethylate solution prepared bydissolving 1.84 g (80 mmol) of sodium in 90 ml of ethanol. The mixturewas stirred at room temperature for 16 hours and at 48° C. for 6 hoursuntil practically no educt was detectable by tlc. A solution of 5.3 g(93 mmol) of acetic acid in 15 ml of ethanol was slowly added dropwisethereto at room temperature while stirring, followed by 120 ml ofethanol/water (1:1). Then the red crystal slurry was suction filtered,washed with 60 ml of ethanol/water (9:1) at 0° C. and washed at roomtemperature with 180 ml of water and at 0° C. with 50 ml ofethanol/water (9:1). After drying at 25 mbar and room temperature for 15hours and at 45° C. under a high vacuum to about 0.16 mbar for 7 hoursthere were obtained 12.6 g (68.5%) of 8'-apo-β-carotenoic acid ethylester as brick-red crystals, m.p. 135° C. A recrystallization inacetone/water was effected analogously to Example 28 and gave 11.5 g(62%) of 8'-apo-β-carotenoic acid ethyl ester as violet, glisteningcrystals with m.p. 139.5° C. and a content according to HPLC of 99.5%.

EXAMPLE 31 8'-Apo-β-carotenoic Acid Methyl Ester

950 mg (41 mmol) of sodium were dissolved in 60 ml of methanol in a 500ml round flask equipped with a magnetic stirrer, a condenser and argongasification. A solution of 6.5 g (12.6 mmol) of12'-methoxy-11',12'-dihydro-8'-apo-β-carotenoic acid methyl ester (LC:93%) in 250 ml of methanol and 20 ml of tert.butyl methyl ether wasadded thereto at room temperature. The mixture was stirred at 60° C. forabout 16 hours, which gave a red suspension tlc (SiO₂): R_(f) =0.45;toluene!. The suspension was cooled to 0° C. and 5 ml of acetic acidwere added thereto. Then the precipitate was suction filtered, washedwith 30 ml of methanol at 0° C., twice with 50 ml, a total of 100 ml, ofwater at room temperature and again with 50 ml of methanol at 0° C. anddried at 40° C. and 12 mbar. This gave 4.3 g (76%) of8'-apo-β-carotenoic acid methyl ester as a red powder, m.p. 145°-146°C.; content according to HPLC: 99.7%; UV (cyclohexane with 3%chloroform): 473 nm (log ε=4.97; E=2096), 448 nm (log ε=5.05; E=2515).

Microanalysis: Calc.: C 83.36% H 9.48% Found: C 83.08% H 9.42%

EXAMPLE 32 4'-Apo-β-carotenoic Acid Ethyl Ester (Neurosporaxanthin EthylEster)

1.16 g (2 mmol) of 8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acidethyl ester (HPLC: 96%) in 80 ml of ethanol were placed under argon in a150 ml round flask. A sodium ethylate solution, prepared by dissolving140 mg (6 mmol) of sodium in 10 ml of ethanol, was added at roomtemperature to the resulting red suspension and the mixture was stirredat 40° C. for about 16 hours tlc (SiO₂): R_(f) =about 0.4-0.5; toluene!.Then the mixture was cooled to room temperature, 1 ml (1.05 g, 16 mmol)of acetic acid was added thereto and the mixture was cooled to 0° C.After stirring the suspension at 0° C. for 2 hours it was suctionfiltered and the filter material was washed with 100 ml of ethanol at-20° C., with 100 ml of water at room temperature and again with 100 mlof ethanol at -20° C. After drying to constant weight under a water-jetvacuum at room temperature there were obtained 800 mg (75% yield) ofneurosporaxanthin ethyl ester, m.p. 144°-145° C. (content according toHPLC: 98.7%). UV (n-hexane): 502 nm (log ε=5.09; E=2173), 471 nm (logε=5.18; E=2857), 450 (log ε=5.06; E=2173), 290 (log ε=4.47; E=563).

Microanalysis: Calc.: C 84.36% H 9.57% Found: C 84.36% H 9.52%

EXAMPLE 33

4'-Apo-β-carotenoic acid ethyl ester (through process from8'-apo-β-carotenal dimethyl acetal and1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene via8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid ethyl ester)

4.80 g (10 mmol) of 8'-apo-β-carotenal dimethyl acetal (contentaccording to HPLC: 97%) and 2.60 g (12 mmol) of1-trimethylsilyloxy-1-ethoxy-2-methyl-1,3-butadiene (content accordingto GC: 94%) were suspended in 100 ml of tert.butyl methyl ether underargon in a 250 ml round flask equipped with a magnetic stirrer. 70 mg(0.5 mmol, 5 mol %) of anhydrous zinc chloride were added to thesuspension at 0° C. and then the mixture was stirred at room temperaturefor 3 hours, which gave a deep red solution tlc (SiO₂): R_(f) =0.2-0.3;toluene!. Then the solution was poured into 100 ml of water andextracted twice with 100 ml each time, a total of 200 ml, of tert.butylmethyl ether, and washed once with 100 ml of water and once with 100 mlof saturated sodium chloride solution. After drying over anhydroussodium sulphate the combined organic phases were concentrated and gave7.3 g of crude 8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid ethylester as a deep red, viscous oil. This residue was dissolved in 250 mlof absolute ethanol and the solution was placed in a 350 ml four-neckedsulphonation flask equipped with a mechanical stirrer, a thermometer andargon gasification. A sodium ethylate solution, prepared by dissolving600 mg (26 mmol) of sodium in 40 ml of absolute ethanol, was now addedto the solution at room temperature and the mixture was stirred at 45°C. for about 16 hours tlc (SiO₂): R_(f) =about 0.4; toluene!. Aftercooling to room temperature 2.4 g (40 mmol) of acetic acid were addedand the mixture was cooled to 0° C. The mixture was suction filtered andwashed twice with 10 ml each time, a total of 20 ml, of ethanol/water(19:1), once with 50 ml of water and a further twice with 10 ml, a totalof 20 ml, of ethanol/water (19:1). After drying under a water-jet vacuumat 45° C. and subsequently under a high vacuum at room temperature therewere obtained 4.2 g (77% yield) of 4'-apo-β-carotenoic acid ethyl esteras brick-red crystals, m.p. 144° C. and a content according to HPLC of97.6%. For further purification, the crude product (4.2 g) was digestedfor about 10 minutes in 120 ml of acetone under argon while stirring atreflux. Then 4 ml of water were added dropwise through the refluxcondenser within about 5 minutes and the mixture was cooled slowly to 0°C. and filtered. After washing the filter material with about 20 ml ofacetone/water (9:1) at 0° C., with 50 ml of water at room temperatureand again with 10 ml of acetone/H₂ O (9:1) at 0° C. the filter materialwas dried under reduced pressure at 50° C. and under a high vacuum atroom temperature to give 4.03 g (75% yield) of neurosporaxanthin ethylester as violet crystals with m.p. 146° C. and a content according toHPLC of 99.4%.

EXAMPLE 34

4'-Apo-β-carotenoic acid ethyl ester (through process from8'-apo-β-carotenal dimethyl acetal and1,1-dimethoxy-2-methyl-1,3-butadiene via8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid methyl ester

4.80 g (10 mmol) of 8'-apo-β-carotenal dimethyl acetal (HPLC: 97%) and1.95 g (15 mmol) of 1,1-dimethoxy-2-methyl-1,3-butadiene (contentaccording to GC: 99.5%) in 100 ml of tert.butyl methyl ether were placedwhile gassing with argon in a 200 ml round flask equipped with amagnetic stirrer. 3 drops (about 35 mg, 2.5 mol %) of boron trifluorideetherate were added while stirring to the resulting suspension at 0° C.Thereby, the suspension dissolved within about 30 minutes and a dark redsolution formed tlc (SiO₂): R_(f) =about 0.1; toluene!. For thehydrolysis, 20 ml of acetic acid/water (9:1) were added at 0° C. and themixture was warmed to room temperature and stirred at this temperaturefor 30 minutes tlc(SiO₂): R_(f) =about 0.25; toluene!. Working-upanalogously to Example 33 gave 6.6 g of crude8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid methyl ester as a deepred, viscous resin. This residue was placed with 200 ml of ethanol in a350 ml four-necked sulphonation flask equipped with a mechanicalstirrer, a thermometer and argon gasification and treated at roomtemperature with a sodium methylate solution prepared by dissolving 600mg (26 mmol) of sodium in 90 ml of ethanol. Subsequently, the mixturewas stirred at 45° C. for about 16 hours tlc (SiO₂): R_(f) =about 0.5;toluene! and cooled to room temperature, and then 2.4 g (40 mmol) ofacetic acid were added dropwise followed by 5 ml of water. Filtrationand washing as described in Example 33 gave 4.8 g (89% yield) of4'-apo-β-carotenoic acid ethyl ester as a red-violet powder, m.p. 144°C.; content according to HPLC: 98.1%. A further purification inacetone/water as described in Example 33 gave 4.44 g (84% yield) of4'-apo-β-carotenoic acid ethyl ester as violet, fine crystals with m.p.146°-147° C. and a content according to HPLC of 99.2%.

EXAMPLE 35

4'-Apo-β-carotenoic acid methyl ester (neurosporaxanthin methyl ester;through process from 8'-apo-β-carotenal dimethyl acetal and1,1-dimethoxy-2-methyl-1,3-butadiene via8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid methyl ester

4.80 g (10 mmol) of 8'-apo-β-carotenal dimethyl acetal (HPLC: 97%) and2.20 g (17 mmol) of 1,1-dimethoxy-2-methyl-1,3-butadiene were suspendedin 100 ml of tert.butyl methyl ether while gassing with argon in a 300ml round flask equipped with a magnetic stirrer and treated at 0° C.with 2 drops (about 25 mg, about 2 mol %) of boron trifluoride etherate.After dissolution of the suspension in about 20-30 minutes (tlc control)20 ml of acetic acid/water (9:1) were added at 0° C. and the mixture wasstirred at room temperature for 50 minutes. Working-up as described inExample 33 gave about 7 g of crude8'-methoxy-7',8'-dihydro-4'-apo-β-carotenoic acid methyl ester as a red,highly viscous oil.

This was suspended in 250 ml of methanol and 20 ml of tert.butyl methylether under argon in a 350 ml four-necked sulphonation flask equippedwith a mechanical stirrer. A sodium methylate solution, prepared bydissolving 700 mg (30 mmol) of sodium in 50 ml of methanol, was added tothe suspension and the mixture was stirred at 50° C. for about 16 hours.Then a solution of 360 mg (15 mmol) of sodium in 15 ml of methanol wasadded thereto and the mixture was refluxed at about 62° C. for 4 hourstlc (SiO₂): R_(f) =about 0.5; toluene!. The mixture was cooled to 0° C.,3.6 g (60 mmol) of acetic acid were added and the mixture was filteredand washed with 30 ml of methanol at 0° C., twice with 25 ml each time,a total of 50 ml, of water and again with 40 ml of methanol at 0° C.After drying at 45° C. under a water-jet vacuum and at room temperatureunder a high vacuum there were obtained 4.60 g (88% yield) of4'-apo-β-carotenoic acid methyl ester as red-violet crystals with m.p.147°-148° C. and a content according to HPLC of 97.8%. Furtherpurification of these crystals with acetone/water as described inExample 33 gave 4.06 g (78% yield) of 4'-apo-β-carotenoic acid methylester as violet crystals with m.p. 150°-151° C. and a content accordingto HPLC of 99.1%; UV (cyclohexane with 3% chloroform): 509 nm (logε=5.07; E=2290), 479 nm (log ε=5.16; E=2830), 292 nm (log ε=4.47;E=574).

Microanalysis: Calc.: C 84.32% H 9.44% Found: C 84.07% H 9.30%

EXAMPLE 36 3',4'-Didehydro-β, ψ-carotenoic Acid Ethyl Ester(Torularhodin Ethyl Ester)

800 mg (1.22 mmol) of 4'-methoxy-β,ψ-caroten-16'-oic acid ethyl esterwere placed in 20 ml of ethanol in a 100 ml round flask equipped with amagnetic stirrer, a condenser and argon gasification. A sodium ethylatesolution, prepared by dissolving 85 mg (3.7 mmol) of sodium in 10 ml ofethanol, was added at room temperature and the mixture was stirred at50° C. for 18 hours and at 70° C. for 30 minutes tlc (SiO₂): R_(f)=about 0.35; toluene!. Then the mixture was cooled to 0° C., acidifiedwith 0.5 ml of acetic acid, suction filtered, washed with cold water andcold ethanol and dried to constant weight at 35° C. under a high vacuum.This gave 640 mg (88% yield) of torularhodin ethyl ester as a deepviolet crystalline powder with m.p. 158°-160° C. and a content of 99.5%according to HPLC. UV (cyclohexane with 3% chloroform): 537 nm (logε=5.12; E=2240), 503 nm (log ε=5.22; E=2815), 480nm (log ε=5.11;E=2178), 321 nm (log ε=4.58; E=642).

EXAMPLE 37 3',4'-Didehydro-β,ψ-carotenoic Acid Methyl Ester(Torularhodin Methyl Ester)

530 mg (0.79 mmol) of 4'-methoxy-β,ψ-caroten-16'-oic acid methyl ester(content according to HPLC=91.3%) were placed in 20 ml of methanol whilegassing with argon in a 50 ml round flask equipped with a magneticstirrer. A sodium methylate solution, prepared by dissolving 150 mg (6.5mmol) of sodium in 15 ml of methanol, was added thereto at roomtemperature and the mixture was stirred at 60° C. for 24 hours tlc(SiO₂): R_(f) =about 0.4; toluene!. Then the mixture was acidified with5 ml of acetic acid and cooled to 0° C., and the solid filtered off,washed twice with in each case 20 ml, a total of 40 ml, of water andtwice with 10 ml, a total of 20 ml, of ice-cold methanol and dried atroom temperature under a high vacuum. This gave 435 mg (91% yield) oftorularhodin methyl ester as a deep violet, crystalline powder with m.p.174°-177° C. and a content of 95.3% according to HPLC. UV (cyclohexanewith 3% chloroform): 537 nm (log ε=5.11; E=2232), 504 nm (log ε=5.21;E=2824), 480 nm (log ε=5.10; E=2200), 321 nm (log ε=4.57; E=642).

EXAMPLE 38 8'-Apo-β-Carotenoic Acid

1.90 g (3.6 mmol) of 12'-methoxy-11,12'-dihydro-8'-apo-β-caroten-8'-oicacid (HPLC: 88.6%) were dissolved in 80 ml of tetrahydrofuran whilegassing with argon in a 150 ml round flask equipped with a magneticstirrer. 1.83 g (16 mmol, 4.5 eq.) of potassium tert.butylate were addedthereto at 0° C. and the mixture was stirred at this temperature for 4hours tlc (SiO₂): R_(f) =about 0.3-0.4; toluene/ethyl acetate (4:1)!.Then the mixture was poured into water and extracted with 50 ml of ethylacetate. The extract was washed with 50 ml of water and 50 ml ofsaturated sodium chloride solution, dried over anhydrous sodium sulphateand filtered. After concentration under reduced pressure there wereobtained 1.8 g of residue, which was digested in 25 ml of hot toluene.After cooling to 0° C. over 18 hours the mixture was filtered, washedwith a small amount of toluene and dried. This gave 570 mg (36% yield)of 8'-apo-β-carotenoic acid as a dark red powder with m.p. 193°-194° C.and a purity of 97.2% according to HPLC after methylation withdiazomethane; UV (cyclohexane with 3% of chloroform): 450 nm (logε=4.96; E=2100), 263 nm (log ε=4.18; E=350).

EXAMPLE 39 8,8'-Diapocarotene-8,8'-dioic Acid Ethyl Ester (CrocetinDiethyl Ester)

5.91 g (12.7 mmol) of11,12,11',12'-tetrahydro-12,12'-dimethoxy-8,8'-diapocarotene-8,8'-dioicacid ethyl ester (content according to HPLC 96.1%) were placed in 150 mlof ethanol in a 350 ml four-necked sulphonation flask equipped with amechanical stirrer, a thermometer and argon gasification. A sodiumethylate solution, prepared by dissolving 920 mg (40 mmol) of sodium in50 ml of ethanol, was added dropwise thereto at room temperature and themixture was stirred at room temperature for 20 hours and at 50° C. for21/2 hours tlc (SiO₂): R_(f) =about 0.35; n-hexane/ethyl acetate (4:1)!.After cooling to room temperature 60 ml of acetic acid were addedthereto, the mixture was cooled to 0° C. and the precipitate wasfiltered off and washed three times with 100 ml each time, a total of300 ml, of water and twice with 50 ml each time, a total of 100 ml, ofethanol at 0° C. After drying (12 mbar at 50° C. and one hour under ahigh vacuum at room temperature) there were obtained 4.02 g (80% yield)of crocetin diethyl ether as an orange powder with m.p. 204°-210° C. anda content of 96.7% according to HPLC. For analysis, a sample wasrecrystallized from hot toluene. The sample obtained had a m.p. of208°-211° C.; content according to HPLC: 97.8%; UV (chloroform): 461 nm(log ε=5.04; E=2877), 433 nm (log ε=5.07; E=3037), 411 nm (log ε=4.87;E=1970).

Microanalysis: Calc.: C 74.97% H 8.39% Found: C 74.72% H 8.45%

EXAMPLE 40 8,8'-Diapocarotene-8,8'-dioic Acid Ethyl Ester (CrocetinDiethyl Ester)

2.18 g (5.2 mmol) of11,12,11',12'-tetrahydro-12,12'-dimethoxy-8,8'-diapocarotene-8,8'-dioicacid methyl ester (content according to HPLC: 99.7%) were placed in 100ml of ethanol in a 200 ml four-necked sulphonation flask equipped with amechanical stirrer, a condenser and argon gasification. A sodiumethylate solution, prepared by dissolving 410 mg (17.8 mmol, 3.5 eq.) ofsodium in 65 ml of ethanol, was added dropwise to the mixture at roomtemperature and the mixture was stirred at room temperature for 16 hoursand at 45°-55° C. for 5 hours tlc (SiO₂): R_(f) =about 0.4;n-hexane/ethyl acetate (4:1)!. Then the mixture was cooled to 0° C., 25ml of acetic acid/water (1:9) were added and the mixture was stirred at0° C. for 1 hour. The precipitate was filtered off, washed twice with 50ml each time, a total of 100 ml, of water and twice with 25 ml eachtime, a total of 50 ml, of ethanol at 0° C. and dried at 12 mbar/40° C.This gave 1.55 g (76% yield) of crocetin diethyl ester as orange-redcrystals, m.p. 206°-210° C.; content according to HPLC: 97.6%.

EXAMPLE 41 8,8'-Diapocarotene-8,8'-dioic Acid Methyl Ester (CrocetinDimethyl Ester)

2.58 g (6.12 mmol) of11,12,11',12'-tetrahydro-12,12'-dimethoxy-8,8'-diapocarotene-8,8'-dioicacid methyl ester (content according to HPLC: 99.7%) were placed in 50ml of methanol in a 200 ml four-necked sulphonation flask equipped witha mechanical stirrer, a dropping funnel, a thermometer and argongasification. A sodium methylate solution, prepared by dissolving 410 mg(18 mmol) of sodium in 45 ml of methanol, was added dropwise to themixture and the mixture was stirred at 50° C. for about 16 hours tlc(SiO₂): R_(f) =about 0.2; n-hexane/ethyl acetate (4:1)!. Then themixture was cooled to 0° C., 25 ml of acetic acid/water (1:9) were addeddropwise, the mixture was stirred for 11/2 hours, filtered and the solidwashed twice with 50 ml each time, a total of 100 ml, of water and twicewith 50 ml each time, a total of 100 ml, of methanol at -10° C. Afterdrying at 12 mbar/40° C. and under a high vacuum at room temperaturethere were obtained 1.95 g (88% yield) of crocetin dimethyl ester as anorange powder with m.p. 212°-219° C. and a content of 97.9% according toHPLC. For the analytical data, a sample was recrystallized from hottoluene. This sample had a m.p. of 219°-222° C.; content according toHPLC: 98.7%; UV (chloroform): 461 nm (log ε=4.98; E=2654), 434 nm (logε=5.00), 410 nm (log ε=4.82; E=1851).

Microanalysis: Calc.: C 74.13% H 7.92% Found: C 73.93% H 8.02%

EXAMPLE 42 4,4'-Diapocarotene-4,4'-dioic Acid Ethyl Ester

240 mg (10.4 mmol) of sodium were dissolved in 70 ml of ethanol whilegassing with argon in a 100 ml round flask equipped with a magneticstirrer. 1.00 g (1.68 mmol) of7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidethyl ester (content according to HPLC: 97.8%) was added thereto at roomtemperature and the mixture was refluxed for about 18 hours tlc (SiO₂):R_(f) =about 0.6; toluene/ethyl acetate (9:1)!. Then the reactionsolution was cooled to room temperature and treated with 20 ml ofethanol/acetic acid (9:1). The separated product was filtered off undersuction, washed three times with 20 ml each time, a total of 60 ml, ofwater and three times with 20 ml each time, a total of 60 ml, ofice-cold ethanol and dried at room temperature under a high vacuum. Thisgave 560 mg (61% yield) of 4,4'-diapocarotene-4,4'-dioic acid ethylester as a dark violet powder with m.p. 188°-189° C. and a content of94.4% according to HPLC. UV (cyclohexane with 3% chloroform): 525 nm(log ε=5.12, E=2524); 490 nm (log ε=5.21; E=3154), 461 nm (log ε=5.07;E=2287), 313 nm (log ε=4.56; E=690).

EXAMPLE 43 4,4'-Diapocarotene-4,4'-dioic Acid Methyl Ester

1.00 g (43 mmol) of sodium was dissolved in 120 ml of methanol whilegassing with argon in a 250 ml round flask equipped with a magneticstirrer. 1.20 g (2.17 mmol) of7,8,7',8'-tetrahydro-8,8'-dimethoxy-4,4'-diapocarotene-4,4'-dioic acidmethyl ester (content according to HPLC: 98.7%) were added thereto atroom temperature and the mixture was refluxed for about 16 hours tlc(SiO₂): R_(f) =about 0.6; toluene/ethyl acetate (9:1)!. The suspensionwas then cooled to room temperature, treated with 20 ml ofmethanol/glacial acetic acid (9:1) and, after cooling to 0° C.,filtered. The filter material was washed three times with 20 ml eachtime, a total of 60 ml, of water and three times with 20 ml each time, atotal of 60 ml, of ice-cold methanol and dried at room temperature undera high vacuum. This gave 0.60 g (55% yield) of4,4'-diapocarotene-4,4'-dioic acid methyl ester as a red powder withm.p. 201° C. and a content of 97.9% according to HPLC. UV (cyclohexanewith 3% chloroform): 525 nm (log ε=5.18, E=3089), 491 nm (log ε=5.24;E=3547), 462 nm (log ε=5.08; E=2440), 313 nm (log ε=4.61; E=834).

The above description was provided to aid in understanding theinvention. Upon reading the entire specification, however, certainvariant embodiments will become obvious to the skilled artisan. Thesevariations are to be considered with the scope and spirit of theinvention which is to only be limited by the claims that follow andtheir equivalents.

What is claimed is:
 1. A process for manufacturing a compound offormula: ##STR25## wherein A is a monovalent conjugated polyene group ora methyl-substituted, monovalent conjugated polyene group,B is abivalent conjugated polyene group or a methyl-substituted, bivalentconjugated polyene group, R¹ and R² each independently is hydrogen ormethyl, and R³ is hydrogen or C₁₋₆ -alkyl, with the--CH═CH--C(R¹)═C(R²)--COOR³ group(s) in each case being situated in theterminal position(s) of the conjugated chain of group A or B, whichprocess comprises:(A) reacting a compound of formula:

    A--CH(OR.sup.4).sub.2                                      II'

or

    (R.sup.4 O).sub.2 HC--B--CH(OR.sup.4).sub.2                II"

wherein A and B are as above, with the --CH(OR⁴)₂ group(s) beingsituated in the terminal position(s) of the conjugated chain of group Aor B, and R⁴ is C₁₋₆ -alkyl, with a compound of formula: ##STR26##wherein R¹ and R² are as above, and R⁵ is C₁₋₆ -alkyl and R⁶ is C₁₋₆-alkyl or tri(C₁₋₆ -alkyl)silyl, or R⁵ and R⁶ both are tri(C₁₋₆-alkyl)silyl, or R⁵ and R⁶ together form 1,2-ethylene or1,3-trimethylene, in the presence of a Lewis acid, and where a compoundof formula III in which R⁵ and R⁶ both are C₁₋₆ -alkyl or both aretri(C₁₋₆ -alkyl)silyl or together form 1,2-ethylene or 1,3-trimethyleneis used, subsequently hydrolyzing the compound formed, so as to form inall cases a compound of the formula: ##STR27## wherein A, B, R¹, R² andR⁴ are as above, with the --CH(OR⁴)--CH₂ C(R¹)═C(R²)COOR⁷ group(s) beingsituated in the terminal position(s) of the conjugated chain of group Aor B, and R⁷ is C₁₋₆ -alkyl, hydrogen, 2-hydroxyethyl or3-hydroxy-n-propyl; (B) cleaving off the R⁴ OH group from the compoundformula IV' or IV" under strong basic conditions; and (C) where there isa difference between groups --COOR⁷ and --COOR³, converting group--COOR⁷ to group --COOR³.
 2. The process according to claim 1, whereinthe reacting involves a compound of the formula:

    R--CH(OR.sup.4).sub.2                                      II

wherein R is a group (a), (b) or (c) ##STR28## in which R⁴ is C₁₋₄-alkyl, R⁸ and R⁹ each independently is hydrogen, a hydroxy group, aprotected hydroxy group, an oxo group or a protected oxo group, m is 0,1, 2, 3 or 4, n is 0 or 1, p is 0, 1 or 2, q is 0, 1, 2 or 3, and r is0, 1 or 2,which is converted after carrying out the multistage processdefined in claim 1 into the corresponding product of formula: ##STR29##wherein R' is as above for R, with the group (R⁴ O)₂ HC-- being replacedby the R³ OOC--C(R²)═C(R¹)--HC═HC-- group when R' is group (c).
 3. Theprocess according to claim 2, wherein R is a group (a) and a protectinggroup is present, the process further comprising cleaving the protectinggroup.
 4. The process according to claim 1, wherein the compound offormula II' or II" is reacted with a compound of formula III in anorganic solvent at temperatures in the range of from about -40° C. toabout 100° C. in the presence of a Lewis acid selected from the groupconsisting of zinc chloride, zinc bromide, titanium tetrachloride,lithium perchlorate, boron trifluoride etherate, and iron(III) chloride.5. The process according to claim 4, wherein the organic solvent isselected from the group consisting of lower aliphatic hydrocarbon,cyclic hydrocarbon, lower, halogenated aliphatic hydrocarbon, loweraliphatic ether, cyclic ether, lower aliphatic nitrile, and aromaticcompounds.
 6. The process according to claim 5, wherein the organicsolvent is selected from the group consisting of n-pentane, n-hexane,cyclohexane, methylene chloride, chloroform, diethyl ether, tert.butylmethyl ether, tetrahydrofuran, acetonitrile and toluene, and thereaction of the compound of formula II' or II" with the compound offormula III is effected in the temperature range of about -20° C. toroom temperature.
 7. The process according to claim 1, wherein thestrong base for the cleavage of the alcohol R⁴ OH from the compound offormula IV' or IV" is an alkali metal alcoholate or an alkali metalhydride.
 8. The process according to claim 7, wherein the cleavage ofthe alcohol R⁴ OH is carried out in a solvent selected from the groupconsisting of an alcohol, an aliphatic ether, a cyclic ether, analiphatic ester, an aromatic, an aliphatic hydrocarbon, a lowerhalogenated aliphatic hydrocarbon and a mixture of an alcohol withanother solvent referred to above.
 9. The process according to claim 7,wherein the cleavage of the alcohol R⁴ OH is carried out using a sodiumalkoxide as the base and the corresponding alkanol as the solvent attemperatures between room temperature and the reflux temperature of therespective reaction mixture.